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Immunophysiology: The Interaction of Hormones, Lymphohemopoietic Cytokines, and the Neuroimmune Axis

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Abstract

The sections in this article are:

1 Proinflammatory Cytokines Regulate the Hypothalamic‐Pituitary Adrenal Axis
2 Inflammatory Cytokines Regulate Secretion of Pituitary Growth Hormone
3 Cytokines and Their Receptors in the Central Nervous System
4 Cells in the Central Nervous System Synthesize Proinflammatory Cytokines
5 Receptors for Interleukin‐1 in the Central Nervous System
6 Receptors for Tumor Necrosis Factor in the Central Nervous System
7 Receptors for Interleukin‐6 in the Central Nervous System
8 Cytokines in the Central Nervous System Regulate Intermediary Metabolism
9 Synergistic Properties of Proinflammatory Cytokines
10 Growth Hormone and Prolactin: Pituitary Hormones Whose Receptors are Members of the Hematopoietin Receptor Superfamily
11 Growth Hormone and Insulin‐Like Growth Factor‐I
12 Insulin‐Like Growth Factor‐I Receptor: A Transmembrane Tyrosine Kinase
13 Immunological Actions of Growth Hormone and Insulin‐Like Growth Factor‐I: The Big Picture
14 Growth Hormone and Insulin‐Like Growth Factor‐I: Hematopoietic Cytokines?
14.1 Erythropoiesis
14.2 Lymphopoiesis
14.3 Myelopoiesis
15 Growth Hormone and Insulin‐Like Growth Factor‐I Demonstrate Classical Properties of Pleiotropic Lymphohemopoietic Cytokines
15.1 Promoting Cell Survival
15.2 Increasing DNA Synthesis
15.3 Enhancing Effector Functions
16 Hematopoietic Actions of Insulin‐Like Growth Factor‐I: Endocrine or Paracrine?
17 Clinical use of Recombinant Growth Hormone
18 Conclusion
Figure 1. Figure 1.

Bacterial infection attenuates somatic growth by inducing release of proinflammatory cytokines from leukocytes. Cytokines, such as IL‐1, TNF‐α, and IL‐6 induce proteolysis and lipolysis and also modulate pituitary GH secretion . The reduction in circulating GH is paralleled by an immediate decline in hepatic IGF‐I secretion and an increase in the serum levels of some IGF binding proteins (IGFBPs). The result is a reduction in the level of IGF‐I at the tissue level. In addition, cytokines have direct effects on hepatic metabolsim (see Table ), including direct inhibitory effects on IGF‐I secretion, induction of acute phase protein synthesis, and glycogenolysis.

Reproduced from
Figure 2. Figure 2.

Effects of vagotomy on the LPS‐induced decrease in locomotor activity (upper) and increase in IL‐1β mRNA in hypothalamus (lower). As shown in the upper graph, subdiaphragmatic vagotomy prevented LPS‐induced sickness as indicated by locomotor activity during a 4‐min test. The lower graph shows that vagotomy prevented the LPS‐induced expression of IL‐1β in murine hypothalamus. Collectively, these data suggest a neural mechanism of communication between the peripheral immune system and CNS.

Adapted from
Figure 3. Figure 3.

Intracellular substrates and signaling pathways in IGF‐I signal transduction in myeloid cells occurs via the transmembrane IGF‐I receptor (IGF‐IR). Insulin‐like growth factor‐I regulates the activation of phosphatidylinositol 3′‐kinase (PI3‐K) in promyeloid cells by inducing the tyrosine phosphorylation of IRS‐1 and IRS‐2. The β subunit of the IGF‐IR directly phosphorylates IRS‐1 and −2 and subsequently activates PI3‐K. There are a number of well‐known downstream targets of PI3‐K, such as GLUT 4 glucose transporters, the 70 Kda ribosomal S6 kinase, some isotypes of protein kinase C, and the protein kinase B (Akt). The question marks signify that the complete pathways between 3′phosphorylated derivatives of PI and the regulation of biologically important genes is not yet fully understood. Insulin‐like growth factor‐I has also been shown to activate the ERK/MAPK pathway by interacting with Shc and the subsequent intermediate proteins, Grb‐2 and Sos. Activation of these pathways by IGF‐I may explain this growth factor's ability to promote survival, proliferation, and differentiation of hematopoietic cells.



Figure 1.

Bacterial infection attenuates somatic growth by inducing release of proinflammatory cytokines from leukocytes. Cytokines, such as IL‐1, TNF‐α, and IL‐6 induce proteolysis and lipolysis and also modulate pituitary GH secretion . The reduction in circulating GH is paralleled by an immediate decline in hepatic IGF‐I secretion and an increase in the serum levels of some IGF binding proteins (IGFBPs). The result is a reduction in the level of IGF‐I at the tissue level. In addition, cytokines have direct effects on hepatic metabolsim (see Table ), including direct inhibitory effects on IGF‐I secretion, induction of acute phase protein synthesis, and glycogenolysis.

Reproduced from


Figure 2.

Effects of vagotomy on the LPS‐induced decrease in locomotor activity (upper) and increase in IL‐1β mRNA in hypothalamus (lower). As shown in the upper graph, subdiaphragmatic vagotomy prevented LPS‐induced sickness as indicated by locomotor activity during a 4‐min test. The lower graph shows that vagotomy prevented the LPS‐induced expression of IL‐1β in murine hypothalamus. Collectively, these data suggest a neural mechanism of communication between the peripheral immune system and CNS.

Adapted from


Figure 3.

Intracellular substrates and signaling pathways in IGF‐I signal transduction in myeloid cells occurs via the transmembrane IGF‐I receptor (IGF‐IR). Insulin‐like growth factor‐I regulates the activation of phosphatidylinositol 3′‐kinase (PI3‐K) in promyeloid cells by inducing the tyrosine phosphorylation of IRS‐1 and IRS‐2. The β subunit of the IGF‐IR directly phosphorylates IRS‐1 and −2 and subsequently activates PI3‐K. There are a number of well‐known downstream targets of PI3‐K, such as GLUT 4 glucose transporters, the 70 Kda ribosomal S6 kinase, some isotypes of protein kinase C, and the protein kinase B (Akt). The question marks signify that the complete pathways between 3′phosphorylated derivatives of PI and the regulation of biologically important genes is not yet fully understood. Insulin‐like growth factor‐I has also been shown to activate the ERK/MAPK pathway by interacting with Shc and the subsequent intermediate proteins, Grb‐2 and Sos. Activation of these pathways by IGF‐I may explain this growth factor's ability to promote survival, proliferation, and differentiation of hematopoietic cells.

References
 1. Abboud S. L., C. R. Bethel, and D. C. Aron. Secretion of insulinlike growth factor I and insulinlike growth factor‐binding proteins by murine bone marrow stromal cells. J. Clin. Invest. 88: 470–475, 1991.
 2. Andus T., J. Bauer, and W. Gerok. Effects of cytokines on the liver. Hepatology 13: 364–375, 1991.
 3. Araki E., M. A. Lipes, M.‐E. Patti, J. C. Brüning, B. III Haag, R. S. Johnson, and C. R. Kahn. Alternative pathway of insulin signalling in mice with targeted disruption of the IRS‐1 gene. Nature 372: 186–190, 1994.
 4. Argetsinger L. S., G. S. Campbell, X. Yang, B. A. Witthuhn, O. Silvenoinen, J. N. Ihle, and C. Carter‐Su. Identification of Jak2 as a growth horm5one receptor‐associated tyrosine kinase. Cell 74: 237–244, 1993.
 5. Argetsinger L. S., G. W. Hsu, M. G. Jr. Myers, N. Billestrup, M. F. White, and C. Carter‐Su. Growth hormone, interferon‐γ, and leukemia inhibitory factor promoted tyrosyl phosphorylation of insulin receptor substrate‐1. J. Biol. Chem. 270: 14685–14692, 1995.
 6. Ref. no. Deleted.
 7. Arkins S., N. Rebeiz, A. Biragyn, D. L. Reese, and K. W. Kelley. Murine macrophages express abundant IGF‐I class I, Ea and Eb transcripts. Endocrinology 133: 2334–2343, 1993.
 8. Arkins S., N. Rebeiz, D. L. Brunke‐Reese, A. Biragyn, and K. W. Kelley. Interferon‐gamma inhibits macrophage insulinlike growth factor‐I synthesis at the transcriptional level. Mol Endocrinol 9: 350–360, 1995.
 9. Arkins S., N. Rebeiz, D. L. Brunke‐Reese, C. Minshall, and K. W. Kelley. The colony stimulating factors induce expression of insulin‐like growth factor‐I messenger ribonucleic acid during hematopoiesis. Endocrinology 136: 1153–1160, 1995.
 10. Ban E., F. Haour, and R. Lenstra. Brain interleukin 1 gene expression induced by peripheral lipopolysaccharide administration. Cytokine 4: 48–54, 1992.
 11. Ban E., G. Milon, N. Prudhomme, G. Fillion, and F. Haour. Receptors for interleukin‐1 (α and β) in mouse brain: mapping and neuronal localization in hippocampus. Neuroscience 43: 21–30, 1991.
 12. Banks W. A., and A. J. Kastin. The interleukins‐1α,‐1β and ‐2 do not acutely disrupt the murine blood‐brain barrier. Int. J. Immunopharmacol. 14: 629–636, 1992.
 13. Banks W. A., A. J. Kastin, and E. G. Gutierrez. Interleukin‐1α in blood has direct access to cortical brain cells. Neurosci. Lett. 163: 41–44, 1993.
 14. Banks W. A., A. J. Kastin, and E. G. Gutierrez. Penetration of interleukin‐6 across the murine blood‐brain barrier. Neurosci. Lett. 179: 53–56, 1994.
 15. Banks W. A., L. Ortiz, S. R. Plotkin, and A. J. Kastin. Human interleukin (IL) 1α, murine IL‐1α and murine IL‐1β are transported from blood to brain in the mouse by a shared saturable mechanism. J. Pharmacol. Exper. Therap. 259: 988–996, 1991.
 16. Barres, B. A., I. K. Hart, H.S.R. Coles, J. F. Burne, J. T. Voyvodic, W. D. Richardson, and M. C. Raff. Cell death and control of cell survival in the oligodendrocyte lineage. Cell 70: 31–46, 1992.
 17. Baserga, R. The double life of the IGF‐I receptor. Receptor 2: 261–266, 1993.
 18. Baserga R. Oncogenes and the strategy of growth factors. Cell 79: 927–930, 1994.
 19. Bazan J. F. Structural design and molecular evolution of a cytokine receptor superfamily. Proc. Natl. Acad. Sci. U.S.A. 87: 6934–6938, 1990.
 20. Bellone G., M. Geuna, A. Carbone, S. Silvestri, R. Foa, G. Emanuelli, and L. Matera. Regulatory action of prolactin on the in vitro growth of CD34 + ve human hemopoietic progenitor cells. J. Cell. Physiol. 163: 221–231, 1995.
 21. Benveniste E. N. Inflammatory cytokines within the central nervous system: Sources, function, and mechanism of action. Am. J. Physiol. 263 (Cell Physiol. 32): C1–C16, 1992.
 22. Benveniste, E. N. Cytokine actions in the central nervous system. Cytokine Growth Factor Rev. 9: 259–275, 1998.
 23. Berczi I. The role of the growth and lactogenic hormone family in immune function. Neuroimmunomodulation 1: 201–216, 1994.
 24. Berczi I., and E. Nagy. Effects of hypophysectomy on immune function. In: Psychoneuroimmunology II, edited by R. Ader, N. Cohen, and D. Felton. San Diego, CA: Academic Press, 1991, p 339–376.
 25. Berkenbosch F., J. van Oers, A. Del Rey, F. Tilders, and H. O. Bersedovsky. Corticotropin‐releasing factor‐producing neurons in the rat activated by interleukin‐1. Science 238: 524–526, 1987.
 26. Besedovsky, H. O., and A. del Rey. Immune‐neuro‐endocrine interactions: facts and hypotheses. Endocr. Rev. 17: 64–102, 1996.
 27. Besedovsky H. O., A. E. del Ray, and E. Sorkin. Lymphokine‐containing supernatants from Con A‐stimulated cells increase corticosterone blood levels. J. Immunol. 126: 385–387, 1981.
 28. Besedovsky H. O., E. Sorkin, M. Keller, and J. Muller. Changes in blood hormone levels during the immune response. Proc. Soc. Exp. Biol. Med. 150: 466–470, 1975.
 29. Beutler B., and A. Cerami. The biology of cachectin/TNF‐a primary mediator of the host response. Ann. Rev. Immunol. 7: 625–655, 1989.
 30. Bhat, R. V., R. DiRocco, V. R. Marcy, D. G. Flood, Y. Zhu, P. Dobrzanski, R. Siman, R. Scott, P. C. Contreras, and M. Miller. Increased expression of IL‐1 beta converting enzyme in hippocampus after ischemia: selective localization in microglia. Neuroscience 16: 4146–4154, 1996.
 31. Billiau A. Interferon β2 as a promoter of growth and differentiation of B cells. Immunol. Today 8: 84–87, 1987.
 32. Binz K., P. Joller, P. Froesch, H. Binz, J. Zapf, and E. R. Froesch. Repopulation of atrophied thymus in diabetic rats by insulin‐like growth factor I. Proc. Natl. Acad. Sci. U.S.A. 87: 3690–3694, 1990.
 33. Bjerknes, R., and D. Aarskog. Priming of human polymorphonuclear neutrophilic leukocytes by insulin‐like growth factor I: increased phagocytic capacity, complement receptor expression, degranulation and oxidative burst. J. Clin. Endocrinol. Metab. 80: 1948–1955, 1995.
 34. Black R. A., S. A. Kronheim, and P. R. Sleath. Activation of interleukin‐1β by a co‐induced protease. FEBS Lett. 247: 386–390, 1989.
 35. Blalock J. E. The syntax of immune‐neuroendocrine communication. Immunol. Today. 15: 504–511, 1994a.
 36. Blalock J. E. The immune system. Our sixth sense. The Immunologist 2: 8–15, 1994.
 37. Blatteis C. M. Neuromodulative actions of cytokines. Yale J. Biol. Med. 63: 133–146, 1990.
 38. Blatteis C. M. The OVLT: The interface between the brain and circulating pyrogens? In: Neuroimmunology of Fever, edited by T. Bartfai and D. Ottoson. Oxford: Pergamon, pp 167, 1992.
 39. Bluet‐Pajot, M.‐T., F. Mounier, A. Slama, C. Videau, C. Kordon, J. Epelbaum, and B. Calvino. The increase in growth hormone ecretion in experimentally induced arthritic rats is an adaptive process involved in the regulation of inflammation. Neuroendocrinology 63: 85–92, 1996.
 40. Bluthé, R. M., C. Beaudu, K. W. Kelley, and R. Dantzer. Differential effects of IL‐1ra on sickness behavior and weight loss induced by IL‐1 in rats. Brain Res. 677: 171–176, 1995.
 41. Bluthé, R. M., M. Bruno, K. W. Kelley, and R. Dantzer. Vagotomy blocks behavioral effects of interleukin‐1 injected via the intraperitoneal route but not via other systemic routes. NeuroReport. 7: 2823–2827, 1996.
 42. Bluthé, R. M., M. Pawloski, S. Suarez, P. Parnet, Q. Pittman, K. W. Kelley, and R. Dantzer. Synergy between tumor necrosis factor and interleukin 1 in the induction of sickness behavior in mice. Psychoneuroendocrinology 19: 197–207, 1994.
 43. Bluthé, R. M., V. Walter, P. Parnet, S. Layé, J. Lestage, D. Verrier, S. Poole, B. E. Stenning, K. W. Kelley, and R. Dantzer. Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism. C.R. Acad. Sci. Paris 317: 499–503, 1994.
 44. Botchkina G. I., M. E. Meistrell, 3rd, Botchkina, Il, and K. J. Tracey. Expression of TNF and TNF receptors (p55 and p75) in the rat brain after focal cerebral ischemia Mol. Med. 3: 765–781, 1997.
 45. Boyer S. H., T. R. Bishop, O. C. Rogers, A. N. Noyes, L. P. Frelin, S. Hobbs. Roles of erythropoietin, insulin‐like growth factor‐I and undifferentiated serum factors in promoting maturation of purified murine erythroid colony‐forming units. Blood 80: 2503–2512, 1992.
 46. Bret‐Dibat, J.‐L., R.‐M. Bluthé, S. Kent, K. W. Kelley, and R. Dantzer. Lipopolysaccharide and interleukin‐1 depress food‐motivated behavior in mice by a vagal‐mediated mechanism. Brain Behav. Immun. 9: 242–246, 1996.
 47. Brown S. L., L. R. Smith, and J. E. Blalock. Interleukin‐1 and interleukin‐2 enhance proopiomelanocortin gene expression in pituitary cells. J. Immunol. 139: 3181–3183, 1987.
 48. Burgering, B. M., and P. J. Coffer. Protein kinase B (c‐Akt) in phosphatidylinositol‐3‐OH kinase signal transduction. Nature 376: 599–602, 1995.
 49. Burgess, W., Q. Liu, J. Zhou, Q. Tang, A. Ozawa, R. VanHoy, S. Arkins, R. Dantzer, and K. W. Kelley. The immune‐endocrine loop during aging: Role of growth hormone and insulin‐like growth factor‐I. Neuroimmunomodulation 6: 56–68, 1999.
 50. Butler, A. A., S. Yakar, I. H. Gewolb, M. Karas, Y. Okubo, and D. LeRoith. Insulin‐like growth factor‐I receptor signal transduction: at the interface between physiology and cell biology. Comp. Biochem. Physiol. 121: 19–26, 1998.
 51. Calduch‐Giner, J. A., A. Sitja‐Bobadilla, P. Alvarez‐Pelitero, and J. Perez‐Sanchez. Growth hormone as an in vitro phagocyte‐activating factor in the gilthead sea bream (Sparus aurata L.). Cell Tiss. Res. 287: 535–540, 1997.
 52. Campbell, G. S., D. J. Meyer, R. Raz, D. E. Levy, J. Schwartz, and C. Carter‐Su. Activation of acute phase response factor (APRF)/Stat3 transcription factor by growth hormone. J. Biol. Chem. 270: 3974–3979, 1995.
 53. Carter D. B., M. R. Deibel, C. J. Dunn, C. S. Tomich, A. L. Laborde, J. L. Slightom, A. E. Berger, M. J. Bienkowski, F. F. Sun, R. N. McEwan, P. K. Harris, A. W. Yem, G. A. Waszak, J. G. Chosay, L. C. Sieu, M. M. Hardee, H. A. Zurcher‐Neely, I. M. Reardon, R. L. Heinrikson, S. E. Truesdell, J. A. Shelly, T. E. Eessalu, B. M. Taylor and D. E. Tracey. Purification, cloning, expression and biological characterization of an interleukin‐1 receptor antagonist protein. Nature 344: 633–638, 1990.
 54. Cheatham, B., and C. R. Kahn. Insulin action and the insulin signaling network. Endocr. Rev. 16: 117–142, 1995.
 55. Cheatham B., C. J. Vlaos, L. Cheatham, L. Wang, J. Blenis, and C. R. Kahn. Phosphatidylinositol 3‐kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Mol. Cell. Biol. 14: 4902–4911, 1994.
 56. Chizzonite R., T. Truitt, P. L. Kilian, A. S. Stern, P. Nunes, K. P. Parker, K. L. Kaffka, A. O. Chua, D. K. Lugg and U. Gubler. Two high‐affinity interleukin 1 receptors represent separate gene products. Proc. Natl. Acad. Sci. U.S.A. 86: 8029–8033, 1989.
 57. Clark R., J. Strasser, S. McCabe, K. Robbins, and P. Jardieu. Insulin‐like growth factor‐I stimulation of lymphopoiesis. J. Clin. Invest. 92: 540–548, 1993.
 58. Coleman, E., T. Elsasser, R. Kemppainen, D. Coleman, and J. Sartin. Effect of endotoxin in pituitary hormone secretion in sheep. Neuroendocrinology 58: 111–122, 1993.
 59. Colotta F., F. Re, M. Muzio, R. Bertini, N. Polentarutti, M. Sironi, J. G. Giri, S. K. Dower, J. E. Sims, and A. Mantovani. Interleukin‐1 type II receptor: a decoy target for IL‐1 that is regulated by IL‐4. Science 261: 472–475, 1993.
 60. Cope A. P., D. Aderka, D. Wallach, M. Kahan, N. R. Chu, F. M. Brennan, and M. Feldmann. Soluble TNF receptor production by activated T lymphocytes: differential effects of acute and chronic exposure to TNF. Immunology 84: 21–30, 1995.
 61. Corpas E., S. M. Harman, and M. R. Blackman. Human growth hormone and human aging. Endocr. Rev. 14: 20–39, 1993.
 62. Cullian, E. B., L. Kwee, P. Nunes, D. J. Shuster, G. Ju, K. W. McIntyre, R. A. Chizzonite, and M. A. Labow. IL‐1 receptor accessory protein is an essential component of the IL‐1 receptor. J. Immunol. 161: 5614–5620, 1998.
 63. Dahn M. S., P. Lange, and L. A. Jacobs. Insulin like growth growth factor‐I production is inhibited in human sepsis. Arch. Surg. 123: 1409–1414, 1988.
 64. Dainiak N. Control of hematopoietic cell growth by somatomedins. Exp. Hematol. 21: 1405–1407, 1993.
 65. Dantzer R. How do cytokines say hello to the brain? Neural versus humoral mediation. Eur. Cytokine Net. 5: 271–273, 1994.
 66. Dantzer, R., R. M. Bluthé, N. Castanon, N. Chauvet, L. Capuron, G. Goodall, K. W. Kelley, J. P. Konsman, S. Layé, P. Parnet, and F. Pousset. Cytokine effects on behavior. In: Psycho‐neuroimmunology, Third Edition, edited by R. Ader, D. L. Felten, and N. Cohen. New York: Academic Press, (in press).
 67. Dardenne, M., M. Do Carmo Leite De Moraes, P. A. Kelly, and M.‐C. Gagnerault. Prolactin receptor expression in human hematopoietic tissues analyzed by flow cytofluorometry. Endocrinology 134: 2108–2114, 1994.
 68. Davila D. R., C.K.E. Edwards III, S. Arkins, J. Simon and K. W. Kelley. Interferon‐γ‐induced priming for secretion of superoxide anion and tumor necrosis factor‐α declines in macrophages from aged rats. FASEB J. 4: 2906–2911, 1990.
 69. DeChiara, T. M., A. Efstratiadis, and E. J. Robertson. A growth‐deficiency phenotype in heterozygous mice carrying an insulin‐like growth factor II gene disrupted by targeting. Nature 345: 78–80, 1990.
 70. De Mello‐Coelho, V., W. Savino, M. C. Postel‐Vinay, and M. Dardenne. Role of prolactin and growth hormone on thymus physiology. Dev. Immunol. 6: 317–323, 1998.
 71. De Simoni, M. G., R. Del Bo, A. De Luigi, S. Simard and G. Forloni. Central endotoxin induces different patterns of interleukin (IL)‐1β and IL‐6 messenger ribonucleic acid expression and IL‐6 secretion in the brain and periphery. Endocrinology 136: 897–902, 1995.
 72. De Simoni, M. G., M. Sironi, A. De Luigi, A. Manfridi, A. Mantovani, and P. Ghezzo. Intracerebroventricular injection of interleukin 1 induces high circulating levels of interleukin 6. J. Exp. Med. 171: 1773–1778, 1990.
 73. Dinarello C. A. Biology of interleukin‐1. FASEB J. 2: 108–115, 1988.
 74. Dinarello C. A. Interleukin‐1 and interleukin‐1 antagonism. Blood 77: 1627–1652, 1991.
 75. Dinarello, C. A. Biological basis for interleukin‐1 in disease. Blood 87: 2095–2147, 1996.
 76. Dinerstein, H., F. Lago, L. Goujon, F. Ferrag, N. Esposito, J. Finidori, P. A. Kelly, and M. C. Postel‐Vinay. The proline‐rich region of the GH receptor is essential for JAK2 phosphorylation, activation of cell proliferation, and gene transcription. Mol. Endocrinol. 9: 1701–1707, 1995.
 77. Dudek H., S. R. Datta, T. F. Franke, M. J. Birnbaum, R. Yao, G. M. Cooper, R. A. Segal, D. R. Kaplan, M. E. Greenberg. Regulation of neuronal survival by the serine‐threonine protein kinase Akt. Science 275: 661–665, 1997.
 78. Ebisui O., J. Fukata, N. Murakami, H. Kobayashi, H. Segawa, S. Muro, I. Hanaoka, Y. Naito, Y. Masui, Y. Ohmoto, H. Imura, and K. Nakao. Effect of IL‐1 receptor antagonist and antiserum to TNF‐α on LPS‐induced plasma ACTH and corticosterone rise in rats. Am. J. Physiol. 266 (Endocrinol. Metab. 29): E986–E992, 1994.
 79. Edwards, C. K. III, S. Arkins, L. M. Yunger, A. Blum, R. Dantzer and K. W. Kelley. The macrophage‐activating properties of growth hormone. Cell. Mol. Neurobiol. 12: 499–510, 1992.
 80. Edwards, C. K. III, S. M. Ghiasuddin, J. M. Schepper, L. M. Yunger and K. W. Kelley. A newly defined property of somatotropin: priming of macrophages for production of superoxide anion. Science 239: 769–771, 1988.
 81. Edwards, C. K. III, S. M. Ghiasuddin, L. M. Yunger, R. M. Lorence, S. Arkins, R. Dantzer and K. W. Kelley. In vivo administration of recombinant growth hormone or interferon‐γ activates macrophages: enhanced resistance to experimental Salmonella typhimurium infection is correlated with the generation of reactive oxygen intermediates. Infect. Immun. 60: 2514–2521, 1992.
 82. Edwards, C. K. III, R. M. Lorence, D. M. Dunham, S. Arkins, L. M. Yunger, J. A. Greager, R. J. Walter, R. Dantzer and K. W. Kelley. Hypophysectomy inhibits the synthesis of tumor necrosis factor a by rat macrophages: partial restoration by exogenous growth hormone or interferon γ. Endocrinology 128: 989–996, 1991.
 83. Edwards, C. K. III, L. M. Yunger, R. M. Lorence, R. Dantzer, K. W. Kelley. The pituitary gland is required for protection against lethal effects of Salmonella typhimurium. Proc. Natl. Acad. Sci. U.S.A. 88: 2274–2277, 1991.
 84. Eisenberg, S. P, R. J. Evans, W. P. Arend, E. Verderber, M. T. Brewer, C. H. Hannum and R. C. Thompson. Primary structure and functional expression from complementary DNA of a human interleukin‐1 receptor antagonist. Nature 343: 341–346, 1990.
 85. Elmquist, J. K., T. E. Scammell, and C. B. Saper. Mechanisms of CNS response to systemic immune challenge: the febrile response. Trends Neurosci. 20: 565–570, 1997.
 86. Engelmann H. D., M. Aderka, M. Rubinstein, D. Rotman and D. Wallach. A tumor necrosis factor‐binding protein purified to homogeneity from human urine protects cells from tumor necrosis factor toxicity. J. Biol. Chem. 264: 11974–11980, 1989.
 87. Everaerdt B., P. Brouckaert and W. Fiers. Recombinant IL‐1 receptor antagonist protects against TNF‐induced lethality in mice. J. Immunol. 152: 5041–5049, 1994.
 88. Fairbairn L. J., G. J. Cowling, B. M. Reipert and T. M. Dexter. Suppression of apoptosis allows differentiation and development of a multipotent hemopoietic cell line in the absence of added growth factors. Cell 74: 823–832, 1993.
 89. Fan, J., D. Char, G. J. Bagby, M. C. Gelato, and C. H. Lang. Regulation of insulin‐like growth factor‐I and IGF‐binding proteins by tumor necrosis factor. Am. J. Physiol. 269 (Regulatory Integrative Comp. Physiol. 38): R1204–1212, 1995.
 90. Fan J., P. E. Molina, M. C. Gelato and C. H. Lang. Differential tissue regulation of insulin‐like growth factor‐I content and binding proteins after endotoxin. Endocrinology 134: 1685–1692, 1994.
 91. Farrar, W. L, P. L. Kilian, M. R. Ruff, J. M. Hill and C. B. Pert. Visualization and characterization of interleukin 1 receptors in brain. J. Immunol. 139: 459–463, 1987.
 92. Feingold K. R., and C. Grunfeld. Tumor necrosis factor alpha stimulates hepatic lipogenesis in the rat in vivo. J. Clin. Invest. 193: 318–325, 1987.
 93. Finck, B. N., R. Dantzer, K. W. Kelley, and R. W. Johnson. In vitro and in vivo evidence for the involvement of tumor necrosis factor‐alpha in the induction of leptin by lipopolysaccharide. Endocrinology 139: 2278–2283, 1998.
 94. Finck, B. N., R. Dantzer, K. W. Kelley, J. Woods, and R. W. Johnson. Central lipopolysaccharide elevates plasma interleukin‐6 concentration by an α‐adrenoreceptor‐mediated mechanism. Am. J. Physiol. 272: (Regulatory Integrative Comp. Physiol. 41) R1880–R1887, 1997.
 95. Finck, B. N., and R. W. Johnson. Anorexia, weight loss and increased plasma interleukin‐6 caused by chronic intracerebroventricular infusion of interleukin‐1beta in the rat. Brain Res. 761: 333–337, 1997.
 96. Finck, B. N., and R. W. Johnson. Tumor necrosis factor (TNF)‐α induces leptin secretion through the p55 TNF receptor. Regul. Integr. Comp. Physiol. 278: R537–R543, 2000.
 97. Fleisher T. A., R. M. White, S. Broder, P. Nissley, R. M. Blaese, J. J. Mulvihill, G. Olive, and T. A. Waldman. X‐linked hypogammaglobulinemia and isolated growth hormone deficiency. New Engl. J. Med. 302: 1429–1434, 1980.
 98. Fontana A., S. Bodmer, and K. Frei. Immunoregulatory factors secreted by astrocytes and glioblastoma cells. Lymphokines 14: 91–121, 1987.
 99. Foster M., E. Montecino‐Rodriguez, R. Clark, and K. Dorshkind. Regulation of B and T cell development by anterior pituitary hormones. Cell Mol. Life Sci. 54: 1076–1082, 1998.
 100. Frei K., D. Nadal, P. Ralph, and A. Fontana. Cytokines in inflammatory brain diseases. Cellular and Cytokine Networks in Tissue Immunity. New York: Wiley‐Liss. pp 91–98.
 101. French R., J. F. Zachary, R. Dantzer, L. S. Frawley, R. Chizzonite, P. Parnet, and K. W. Kelley. Dual expression of p80 type I and p68 type II interleukin‐1 receptors on anterior pituitary cells synthesizing growth hormone. Endocrinology 137: 4027–4036, 1996.
 102. French R. A., R. W. VanHoy, R. Chizzonite, J. F. Zachary, R. Dantzer, P. Parnet, R. M. Bluthe, and K. W. Kelley. Expression and localization of p80 and p68 interleukin‐1 receptor proteins in the brain of adult mice. J. Neuroimmunol 93: 194–202, 1999.
 103. Freund, G. G., D. T. Kulas, and R. A. Mooney. Insulin and IGF‐I increase mitogenesis and glucose metabolism in the multiple myeloma cell line, RPMI 8226. J. Immunol. 151: 1811–1820, 1993.
 104. Frost, R. A., C. H. Lang, and M. C. Gelato. Transient exposure of human myoblasts to tumor necrosis factor‐alpha inhibits serum and insulin‐like growth factor‐I stimulated protein synthesis. Endocrinology 138: 4153–4159, 1997.
 105. Fu, Y.‐K., S. Arkins, G. Fuh, B. C. Cunningham, J. A. Wells, S. Fong, M. J. Cronin, R. Dantzer, and K. W. Kelley. Growth hormone augments superoxide anion secretion of human neutrophils by binding to the prolactin receptor. J. Clin. Invest. 89: 451–457, 1992.
 106. Fu, Y.‐K., S. Arkins, Y. M. Li, R. Dantzer, and K. W. Kelley. Reduction in superoxide anion secretion and bactericidal activity of neutrophils from aged rats: reversal by the combination of gamma interferon and growth hormone. Infect. Immun. 62: 1–8, 1994.
 107. Fu, Y.‐K, S. Arkins, B. S. Wang, K. W. Kelley. A novel role of growth hormone and insulin‐like growth factor: Priming neutrophils for superoxide anion secretion. J. Immunol. 146: 1602–1608, 1991.
 108. Fukata J., Y. Usui, Y. Nakai, and H. Imura. Effects of recombinant human interleukin‐1α,‐1β,‐2 and ‐6 on ACTH synthesis and release in the mouse pituitary tumor line AtT‐20. J. Endocrinol. 122: 33–39, 1989.
 109. Gagnerault, M.‐C., M.‐C. Postel‐Vinay, and M. Dardenne. Expression of growth hormone receptors in murine lymphoid cells analyzed by flow cytofluorometry. Endocrinology. 137: 1719–1726, 1996.
 110. Gaillard, R. C. Cytokines in the neuroendocrine system. Int. Rev. Immunol. 17: 181–216, 1998.
 111. Gatti S., and T. Bartfai. Induction of tumor necrosis factor‐alpha messenger RNA in the brain after peripheral endotoxin treatment‐comparison with interleukin‐1 family and interleukin‐6. Brain Res. 624: 291–294, 1993.
 112. Geenen V., I. Achour, F. Robert, E. Vandersmissen, J. C. Sodoyez, M. P. Defresne, J. Boniver, P. J. Lefebvre, and P. Franchimont. Evidence that insulin‐like growth factor 2 (IGF‐2) is the dominant thymic peptide of the insulin superfamily. Thymus 21: 115–127, 1993.
 113. Gibson L. F., D. Piktel, and K. S. Landreth. Insulin‐like growth factor‐I potentiates expansion of interleukin‐7 dependent pro‐B cells. Blood 82: 3005–3011, 1993.
 114. Gjerset R. A., J. Yeatgin, S. K. Volkman, V. Vila, J. Arya, and M. Haas. Insulin‐like growth factor‐I supports proliferation of autocrine thymic lymphoma cells with a pre‐T cell phenotype. J. Immunol. 145: 3497–3501, 1990.
 115. Goehler L. E., R. P. Gaykema, S. E. Hammack, S. F. Maier, and L. R. Watkins. Interleukin‐1 induces c‐Fos immunoreactivity in primary afferent neurons of the vagus nerve. Brain Res. 804: 306–310, 1998.
 116. Goehler L. E., R. P. Gaykema, K. T. Nguyen, J. E. Lee, F. J. Tilders, S. F. Maier, and L. R. Watkins. Interleukin‐1beta in immune cells of the abdominal vagus nerve: a link between the immune and nervous system. J. Neurosci. 19: 2799–2806, 1999.
 117. Golde D. W., N. Bersh, and C. H. Li. Growth hormone: species specific stimulation of erythropoiesis in vitro. Science. 96: 1112–1113, 1977.
 118. Goodwin R. G., D. Anderson, R. Jerzy, T. Davis, C. I. Brannan, N. G. Copeland, N. A. Jenkins and C. A. Smith. Molecular cloning and expression of the type 1 and type 2 murine receptors for tumor necrosis factor. Mol. Cell. Biol. 11: 3020–3026, 1991.
 119. Gouilleux F., C. Pallard, I. Dusanter‐Fourt, H. Wakao, L. A. Haldosen, G. Norstedt, D. Levy, And B. Groner. Prolactin, growth hormone, erythropoietin and granulocyte‐macrophage colony stimulating factor induce MGF‐Stat5 DNA binding activity. EMBO J. 14: 2005–2013, 1995.
 120. Goujon E., P. Parnet, S. Layé, C. Combe, K. W. Kelley and R. Dantzer. Stress downregulates lipopolysaccharide‐induced expression of pro‐inflammatory cytokines in the spleen, pituitary and brain of mice. Brain Behav. Immun. 9: 292–303, 1995.
 121. Gradient R. A., and U. Otten. Differential expression of interleukin‐6 (IL‐6) and interleukin‐6 receptor (IL‐6R) mRNAs in rat hypothalamus. Neurosci. Lett. 153: 13–16, 1993.
 122. Gray P. W., K. Barrett, D. Chantry, M. Truner and M. Feldman. Cloning of human tumor necrosis factor (TNF) receptor cDNA and expression of recombinant soluble TNF‐binding protein. Proc. Natl. Acad. Sci. U.S.A. 87: 7380–7384, 1990.
 123. Greenfeder S. A., P. Nunes, L. Kwee, M. Labow, R. A. Chizzonite, and G. Ju. Molecular cloning and characterization of a second subunit of the interleukin‐1 receptor complex. J. Biol. Chem. 270: 13757–13765, 1995.
 124. Grunfeld C., and K. R. Feingold. Tumor necrosis factor, cytokines, and hyperlipidemia of infection. Trend Endocrinol. Met. 2: 213–219, 1991.
 125. Grunfeld C., and D. P. Kotler. Pathophysiology of the AIDS wasting syndrome. In: Aids in Clinical Review, edited by P. Volberding, and M. A. Jacobson, p 191–224, 1992.
 126. Grunfeld C., and M. A. Palladino. Tumor necrosis factor: immunologic, antitumor, metabolic, and cardiovascular activities. Adv. Intern. Med. 35: 45–72, 1990.
 127. Guler H. P., J. Zapf, E. Scheiwiller, and E. R. Froesch. Recombinant human insulin‐like growth factor I stimulates growth and has distinct effects on organ size in hypophysectomized rats. Proc. Natl. Acad. Sci. U.S.A. 85: 4889–4893, 1988.
 128. Gustafson T. A., W. He, A. Craparo, C. D. Schaub and T. J. O'Neill. Phosphotyrosine‐dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non‐SH2 domain. Mol. Cell. Biol. 15: 2500–2508, 1995.
 129. Gutierrez E. G., W. A. Banks and A. J. Kastin. Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. J. Neuroimmunol. 47: 169–176, 1993.
 130. Hill M. R., and R. E. McCallum. Identification of tumor necrosis factor as a transcriptional regulator of the phosphoenolpyruvate carboxykinase gene following endotoxin treatment in mice. Infect. Immunol. 60: 4040–4050, 1992.
 131. Haour F. G., E. M. Ban, G. M. Milon, D. Baran and G. M. Fillion. Brain interleukin 1 receptors: Characterization and modulation after lipopolysaccharide injection. Prog. Neuro Endocrin Immunology 3: 196–204, 1991.
 132. Hirai K., M. Miyamasu, M. Yamaguchi, K. Nakajima, T. Ohtoshi, T. Koshino, T. Takaishi, Y. Morita and K. Ito. Modulation of human basophil histamine release by insulin‐like growth factors. J. Immunol. 150: 1503–1508, 1993.
 133. Hochberg Z., P. Hertz, G. Maor, J. Oiknine, and M. Aviram. Growth hormone and insulin‐like growth factor‐I increase macrophage uptake and degradation of low density lipoprotein. Endocrinology 131: 430–435, 1992.
 134. Hooghe‐Peters, E. L., and R. Hooghe. Growth Hormone, Prolactin and IGF‐I as Lymphohemopoietic Cytokines. Austin, TX: R. G. Landes Company, 1995.
 135. Hopkins S. J., and N. J. Rothwell. Cytokines and the nervous system I: expression and recognition. Trends Neurosci. 18: 83–88, 1995.
 136. Hotamisligil G. S., D. L. Murray, L. N. Choy, and B. M. Spiegelman. Tumor necrosis factor α inhibits signaling from the insulin receptor. Proc. Natl. Acad. Sci. U.S.A. 91: 4854–4858.
 137. Jansky L., S. Vybiral, D. Pospiŝilova, J. Roth, E. Zeisberger and J. Kaminková. Production of systemic and hypothalamic cytokines during the early phase of endotoxin fever. Neuroendocrinology 62: 55–61, 1995.
 138. Jardieu P., R. Clark, D. Mortensen and K. Dorshkind. In vivo administration of insulin‐like growth factor‐I stimulates primary B lymphopoiesis and enhances lymphocyte recovery after bone marrow transplantation. J. Immunol. 152: 4320–4327, 1994.
 139. Jirillo E., V. Covelli, A. B. Maffione, B. Greco, S. Pece, D. Fumarola, S. Antonaci and C. De Simone. Endotoxins, cytokines, and neuroimmune networks with special reference to HIV infection. Ann. NY Acad. Sci. 741: 174–184, 1994.
 140. Johnson E. W., L. A. Jones and R. W. Kozak. Expression and function of insulin‐like growth factor receptors on anti‐CD3‐activated human T lymphocytes. J. Immunol. 148: 63–71, 1992.
 141. Johnson, R. W., S. Arkins, R. Dantzer, and K. W. Kelley. Hormones, lymphohemopoietic cytokines and the neuroimmune axis. Comp. Biochem. Physiol. 116: 183–201, 1996.
 142. Johnson R. W., M. J. Propes, and Y. Shavit. Corticosterone modulates the behavioral and metabolic effects of lipopolysaccharide. Am. J. Physiol. 270 (Regulatory Integrative Comp. Physiol): R192–R198, 1996.
 143. Johnston J. A., L.‐M. Wang, E. P. Hanson, X‐J. Sun, M. F. White, S. A. Oakes, J. H. Pierce and J. J. O'Shea. Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. Potential role of JAK Kinases. J. Biol. Chem. 270: 28527–28530, 1995.
 144. Jones, J. I., and D. R. Clemmons. Insulin‐like growth factors and their binding proteins: biological actions. Endocr. Rev. 16: 3–34, 1995.
 145. Kakucska I., Y. Qi, B. D. Clark and R. M. Lechan. Endotoxin‐induced corticortropin‐releasing hormone gene expression is the hypothalamic paraventricular nucleus is mediated centrally by interleukin‐1. Endocrinology 133: 815–821, 1993.
 146. Kaplan D. Autocrine secretion and the physiological concentration of cytokines. Immunol. Today. 17: 303–304, 1996.
 147. Kasting, N. W. and J. B. Martin. Altered release of growth hormone and thyrotropin induced by endotoxin in the rat. Am. J. Physiol. 243: E332–E337, 1982.
 148. Katsuura G., A. Arimura, K. Koves and P. E. Gottschall. Involvement of Organum vasculosum of lamina terminalis and preoptic area in interleukin 1β‐induced ACTH release. Am. J. Physiol. 258 (Endocrinol. Metab. 21): E163–E171, 1990.
 149. Keegan A. D., K. Nelms, M. White, L.‐M. Wang, J. H. Pierce and W. E. Paul. An IL‐4 receptor region containing an insulin receptor motif is important for IL‐4‐mediated IRS‐1 phosphorylation and cell growth. Cell 76: 811–820, 1994.
 150. Kelley K. W. Growth hormone, lymphocytes and macrophages. Biochem. Pharmacol. 38: 705–713, 1989.
 151. Kelley, K. W, S. Arkins and Y. M. Li. Growth hormone, prolactin, and insulin‐like growth factor: New jobs for old players. Brain, Behav. Immun. 6: 317–326, 1992.
 152. Kelley K. W., S. Brief, H. J. Westly, J. Novakofski, P. J. Bechtel, J. Simon, E. B. Walker. GH3 pituitary adenoma implants can reverse thymic aging. Proc. Natl. Acad. Sci. U.S.A. 83: 5663–5667, 1986.
 153. Ref. no. Deleted.
 154. Kent S., R. M. Bluthé, R. Dantzer, A. J. Hardwick, K. W. Kelley, N. J. Rothwell and J. L. Vannice. Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin 1. Proc. Natl. Acad. Sci. U.S.A. 89: 9117–9120, 1992.
 155. Kent S., R. M. Bluthé, K. W. Kelley and R. Dantzer. Sickness behavior as a new target for drug development. Trends Pharmacol. Sci. 131: 24–28, 1992.
 156. Kent S., J. L. Bret‐Dibat, K. W. Kelley and R. Dantzer. Mechanisms of sickness‐induced decreases in food‐motivated behavior. Neurosci. Biobehav. Rev. 20: 171–175, 1996.
 157. Kent S., F. Rodriguez, K. W. Kelley and R. Dantzer. Anorexia induced by microinjection of IL‐1β in the ventromedial hypothalamus of the rat. Physiol. Behav. 56: 1031–1036, 1994.
 158. Kimata, H., and M. Fujimoto. Growth hormone and insulin‐like growth factor‐I induce immunoglobulin (Ig)E and IgG4 production by human B cells. J. Exp. Med. 180: 727–732, 1994.
 159. Kincade P. W. B lymphopoiesis: Global factors, local control. Proc. Natl. Acad. Sci. U.S.A. 91: 2888–2889, 1994.
 160. Kinouchi K., G. Brown, G. Pasternak and D. B. Donner. Identification and characterization of receptors for tumor necrosis factor‐α in the brain. Biochem. Biophys. Res. Comm. 181: 1532–1538, 1991.
 161. Kishimoto T., T. Taga and S. Akira. Cytokine signal transduction. Cell 76: 253–262, 1994.
 162. Klasing K. C. Nutritional aspects of leukocytic cytokines. J. Nutr. 118: 1436–1446, 1988.
 163. Kluger M. J. Fever: role of pyrogens and cryogens. Physiol. Rev. 71: 93–127, 1991.
 164. Knyszynski A., S. Adler‐Kunin, A. Globerson. Effects of growth hormone on thymocyte development from progenitor cells in the bone marrow. Brain Behav. Immun. 6: 327–340, 1992.
 165. Kohno T., M. T. Brewer, S. L. Baker, P. E. Schwartz, M. W. King, K. K. Hale, C. H. Squires, R. C. Thompson and J. L. Vannice. A second tumor necrosis factor receptor gene product can shed a naturally occurring tumor necrosis factor inhibitor. Proc. Natl. Acad. Sci. U.S.A. 87: 8331–8335, 1990.
 166. Konsman, J. P., K. W. Kelley, and R. Dantzer. Temporal and spatial relationships between lipopolysaccharide‐induced expression of Fos, interleukin‐1beta and inducible nitric oxide synthase in rat brain. Neuroscience 89: 535–548, 1999.
 167. Kooijman R., E. L. Hooghe‐Peters and R. Hooghe. Prolactin, growth hormone and insulin‐like growth factor I in the immune system. Adv. Immunol. 63: 377–454, 1996.
 168. Kooijman R., L. E. Scholtens, G. T. Rijkers and B.J.M. Zegers. Differential expression of type I insulin‐like growth factor receptors in different stages of human T cells. Eur. J. Immunol. 25: 931–935, 1995a.
 169. Kooijman R., L. E. Scholtens, G. T. Rijkers and B.J.M. Zegers. Type I insulin‐like growth factor receptor expression in different developmental stages of human thymocytes. J. Endocrinol. 147: 203–209, 1995b.
 170. Kooijman R., J. J. Lauf, A. C. Kappers and G. T. Rijkers. Insulin‐like growth factor induces phosphorylation of immunoreactive insulin receptor substrate and its association with phosphatidylinositol‐3 kinase in human thymocytes. J. Exp. Med. 182: 593–597, 1995.
 171. Kurtz A., J. Zapf, K.‐U. Eckardt, G. Clemons, E. R. Froesch, and C. Bauer. Insulin‐like growth factor I stimulates erythropoiesis in hypophysectomized rats. Proc. Natl. Acad. Sci. U.S.A. 85: 7825–7829, 1988.
 172. Landreth K. S., R. Narayanan, and K. Dorshkind. Insulin‐like growth factor‐I regulates pro‐B cell differentiation. Blood 80: 1207–1212, 1992.
 173. Lang C. H., V. Pollard, J. Fan, L. D. Traber, D. L. Traber, R. A. Frost, M. C. Gelato, and D. S. Prough. Acute alterations in growth hormone‐insulin‐like growth factor axis in humans injected with endotoxin. Am. J. Physiol. 273, (Regulatory Integrative Comp. Physiol. 42): R371–378, 1997.
 174. Layé, S., R. Bluthé, S. Kent, C. Combe, C. Médina, P. Parnet, K. W. Kelley, and Dantzer, R. Subdiaphragmatic vagotomy blocks induction of IL‐1β mRNA in mice brain in response to peripheral LPS. Am. J. Physiol. 268 (Regulatory Integrative Comp. Physiol. 37): R1327–R1331, 1995.
 175. Layé, S., E. Goujon, C. Combe, R. VanHoy, K. W. Kelley, P. Parnet, and R. Dantzer. Effects of lipopolysaccharide and glucocorticoids on expression of interleukin‐1β converting enzyme in the ituitary and brain of mice. J. Neuroimmunol. 68: 61–66. 1996
 176. Layé, S., P. Parnet, E. Goujon, and R. Dantzer. Peripheral administration of lipopolysaccharide induces the expression of cytokine transcripts in the brain and pituitary of mice. Mol. Brain Res. 27: 157–162. 1994
 177. Lazarus D. D., S. F. Lowry, and L. L. Moldawer. Cytokines acutely decrease circulating insulin‐like growth factor‐I (IGF‐I) and IGF binding protein‐3 (IGFBP‐3). Archiv. Surg. 129: 92–94. 1992
 178. Lazarus, D. D., L. L. Moldawer, and S. F. Lowry. Insulin‐like growth factor‐I activity is inhibited by interleukin‐1a, tumor necrosis factor‐a and interleukin‐6. Lymph. Cyt. Res. 12: 219–223, 1993.
 179. Ref. no. Deleted.
 180. Li Y. M., S. Arkins, R. H. McCusker, Jr. S. M. Donovan, Q. Liu, S. Jayaraman, R. Dantzer, and K. W. Kelley. Macrophages synthesize and secrete a 25 KDa protein that binds insulin‐like growth factor‐I. J. Immunol. 156: 64–72, 1996.
 181. Li Y. M., D. H. Schacher, Q. Liu, S. Arkins, N. Rebeiz, R. H. Jr McCusker, R. Dantzer and K. W. Kelley. Regulation of myeloid growth and differentiation by the insulin‐like growth factor I receptor. Endocrinology 138: 362–368, 1997.
 182. Liao J., J. A. Keiser, W. E. Scales, S. L. Kunkel, and M. J. Kluger. Role of epinephrine in TNF and IL‐6 production from isolated perfused rat. Liver. Am. J. Physiol. 268: R896–R901, 1995.
 183. Lienhard G. E. Life without the IRS. Nature 372: 128–129, 1994.
 184. Ref. no. Deleted.
 185. Ling P. R., N. W. Istfan, E. Colon, and B. R. Bistrian. Differential effects of interleukin‐1 receptor antagonist in cytokine‐ and endotoxin‐treated rats. Am. J. Physiol. 268: (Endocrinol. Metab. 31): E255–E261, 1995.
 186. Linthorst, A.C.E., C. Flachskamm, F. Holsboer, and J.M.H.M. Reul. Local administration of recombinant human interleukin‐1β in the rat hippocampus increases serotonergic neurotransmission, hypothalamic‐pituitary‐adrenocortical axis activity, and body temperature. Endocrinology 135: 520–532, 1994.
 187. Liu Q., S. Arkins, A. Biragyn, C. Minshall, P. Parnet, R. Dantzer, and K. W. Kelley. Competitive reverse transcriptase‐polymerase chain reaction using a synthetic internal RNA standard to quantitate transcripts for leukocyte‐derived hormones. Neuroimmunomodulation 1: 33–41, 1994.
 188. Liu, Q, W. Ning, R Dantzer, G. G. Freund, K. W. Kelley. Activation of protein kinase C‐zeta and phosphatidylinositol 3′‐kinase and promotion of macrophage differentiation by insulin‐like growth factor‐I. J. Immunol. 160: 1393–1401, 1998.
 189. Liu, Q, D. Schacher, C. Hurth, G. G. Freund, R. Dantzer, K. W. Kelley. Activation of phosphatidylinositol 3′‐kinase by insulin‐like growth factor‐I rescues promyeloid cells from apoptosis and permits their differentiation into granulocytes J. Immunol. 159: 829–837, 1997.
 190. Liu, Q, R. W. VanHoy, J. H. Zhou, R. Dantzer, G. G. Freund, K. W. Kelley. Elevated cyclin E levels, inactive retinoblastoma protein, and suppression of the p27(KIP1) inhibitor characterize early development of promyeloid cells into macrophages. Mol. Cell. Biol. 19: 6229–6239, 1999.
 191. Loetscher H., Y. C. Pan, H. W. Lahm, M. Brockhaus and W. Lesslauer. Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell 61: 351–359, 1990.
 192. Lumpkin, M. Regulation of growth hormone and prolactin secretion by interleukin‐1. In: Stress and Related Disorders from Adaptation to Dysfunction edited by A. R. Genazzani, G. Nappi, F. Petraglia, and E. Martignoni. Park Ridge: Parthenon, 1990, p 17–30.
 193. Manfredi, R., F. Tumietto, L. Azzaroli, A. Zucchini, F. Chiodo, and G. Manfredi. Growth hormone (GH) and the immune system: impaired phagocytic function in children with idiopathic GH deficiency is corrected by treatment with biosynthetic GH. J. Ped. Endocrinol. 7: 245–251, 1994.
 194. Martin, S. J., and D. R. Green. Protease activation during apoptosis: death by a thousand cuts? Cell 82: 349–352, 1995.
 195. McCarthy D. O., and J. M. Daun. The role of prostaglandins in interleukin‐1 induced gastroparesis. Physiol. Behav. 52: 351–353, 1992.
 196. McCubrey J. A., L. S. Steelman, M. W. Mayo, P. A. Algate, R. A. Dellow and M. Kaleko. Growth promoting effects of insulin‐like growth factor‐I (IGF‐I) on hematopoietic cells: overexpression of introduced IGF‐I receptor abrogates interleukin‐3 dependency of murine factor‐dependent cells by a ligand‐dependent mechanism. Blood 78: 921–929, 1991.
 197. McGeehan G. M., J. D. Becherer, R. C. Bast, C. M. Boyer, B. Champion, K. M. Conolly, J. G. Conway, P. Furdon, S. Karp, S. Kidao, A. B. McElroy, J. Nichols, K. M. Pryzwansky, F. Schoenen, L. Sekut, A. Truesdale, M. Verghese, J. Warner and J. P. Ways. Regulation of tumor necrosis factor‐α processing by a metalloproteinase inhibitor. Nature 370: 558–561, 1994.
 198. McHugh K. J., S. M. Collins, and H. P. Weingarten. Central interleukin‐1 receptors contribute to suppression of feeding after acute colitis in the rat. Am. J. Physiol. 266 (Regulatory Integrative Comp. Physiol. 35): R1659–R1663, 1994.
 199. McMahan C. J., J. L. Slack, B. Mosley, D. Cosman, S. D. Lupton, L. L. Brunton, C. E. Grubin, J. M. Wignall, N. A. Jenkins, C. I. Brannan, N. G. Copeland, K. Huebner, C. M. Croce, L. A. Cannizzarro, D. Benjamin, S. K. Dower, M. K. Spriggs, and J. E. Sims. A novel IL‐1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types. EMBO J. 10: 2821–2832, 1991.
 200. Memon R. A., K. R. Feingold, and C. Grunfeld. The effects of cytokines on intermediary metabolism. The Endocrinologist 4: 59–63, 1994.
 201. Merchav S., I. Silvian‐Drachsler, I. Tatarsky, M. Lake and A. Skottner. Comparative studies of the erythroid‐potentiating effects of biosynthetic human insulin‐like growth factors‐I and ‐II. Endocrinology 73: 447–452, 1992.
 202. Merchav S., I. Tatarsky, Z. Hochberg. Enhancement of erythropoiesis in vitro by human growth hormone is mediated by insulin‐like growth factor I. Brit. J. Hematol. 70: 267–271, 1988a.
 203. Merchav S., I. Tatarsky and Z. Hochberg. Enhancement of human granulopoiesis in vitro is mediated biosynthetic insulin‐like growth factor‐I/somatomedin C and human growth hormone. J. Clin. Invest. 81: 791–797, 1988b.
 204. Merimee T. J., M. B. Grant, C. M. Broder and L.‐L. Cavalli‐Sforza. Insulin‐like growth factor secretion by human B‐lymphocytes: a comparison of cells from normal and pygmy subjects. J. Clin. Endocrinol. Metab. 69: 978–984, 1989.
 205. Metcalf D., and N. Nicola. The Hemopoietic Colony‐Stimulating Factors. From Biology to Clinical Applications. New York: University of Cambridge, 1995.
 206. Meyer, D. J., G. S. Campbell, B. H. Cochran, L. S. Argetsinger, A. C. Larner, D. S. Finbloom, C. Carter‐Su, and J. Schwartz. Growth hormone induces a DNA binding factor related to the interferon‐stimulated 91‐kDA transcription factor. J. Biol. Chem. 269: 4701–4704, 1994.
 207. Ref. no. Deleted.
 208. Minshall C., S. Arkins, R. Dantzer, G. G. Freund, and K. W. Kelley. Phosphatidylinositol 3′‐kinase, but not S6‐kinase, is required for insulin‐like growth factor‐I and IL‐4 to maintain expression Bcl‐2 and promote survival of myeloid progenitors. J. Immunol. 162: 4542–4549, 1999.
 209. Minshall C., S. Arkins, G. G. Freund, and K. W. Kelley. Requirement for phosphatidylinositol 3′‐kinase to protect hematopoietic progenitors against apoptosis depends upon the extracellular survival factor. J. Immunol. 156: 939–947, 1996.
 210. Minshall, C. S. Arkins, J. Straza, J. Conners, R. Dantzer, G. G. Freund, and K. W. Kelley. IL‐4 and insulin‐like growth factor‐I inhibit the decline in Bcl‐2 and promote the survival of IL‐3‐deprived myeloid progenitors. J. Immunol. 159: 1225–1232, 1997.
 211. Moltz H. Fever: causes and consequences. Neurosci. Biobehav. Rev. 17: 237–269, 1993.
 212. Montecino‐Rodriguez, E., R. Clark, K. Dorshkind. Effects of insulin‐like growth factor administration and bone marrow transplantation on thymopoiesis in aged mice. Endocrinology 139: 4120–4126, 1998.
 213. Ref. no. Deleted.
 214. Murphy W. J., S. K. Durum, M. R. Anver, and D. L. Longo. Immunologic and hematologic effects of neuroendocrine hormones. Studies on DW/J dwarf mice. J. Immunol. 148: 3799–3805, 1992.
 215. Murphy W. J., S. K. Durum, and D. L. Longo. Role of neuroendocrine hormones in murine T cell development. Growth hormone exerts thymopoietic effects in vivo. J. Immunol. 149: 3851–3857, 1992a.
 216. Murphy W. J., S. K. Durum, and D. L. Longo. Human growth hormone promotes engraftment of murine or human T cells in severe combined immunodeficient mice. Proc. Natl. Acad. Sci. USA. 89: 4481–4485, 1992b.
 217. Murphy W. J., S. K. Durum, and D. L. Longo. Differential effects of growth hormone and prolactin on murine T cell development and function. J. Exp. Med. 178: 231–236, 1993.
 218. Murphy W. J., G. Tsarfaty, and D. L. Longo. Growth hormone exerts hematopoietic growth‐promoting effects in vivo and partially counteracts the myelosuppressive effects of azidothymidine. Blood 80: 1443–1447, 1992.
 219. Muta K., and S. B. Krantz. Apoptosis of human erythroid colony‐forming cells is decreased by stem cell factor and insulin‐like growth factor I as well as erythropoietin. J. Cell. Physiol. 156: 264–271, 1993.
 220. Navarra R. A., S. Tsagarakis, M. S. Faria, L. H. Rees, G. M. Besser and A. B. Grossman. Interleukins‐1 and ‐6 stimulate the release of corticotropin‐releasing hormone‐41 from rat hypothalamus in vitro via the eicosanoid cyclooxygenase pathway. Endocrinology 128: 37–44, 1991.
 221. Nonogaki K., G. M. Fuller, N. L. Fuentes, A. H. Moser, I. Staprans, C. Grunfeld and K. R. Feingold. Interleukin‐6 stimulates hepatic triglyceride secretion in rats. Endocrinology 136: 2143–2149, 1995.
 222. Nophar Y., O. Kemper, and C. Brakebusch. Soluble forms of tumor necrosis factor receptors (TNF‐R‐s). The cDNA for the type I TNF‐R clones using amino acid sequence data of its soluble form, encodes both the cell surface and a soluble form of the receptor. EMBO J. 9: 3269–3275, 1990.
 223. Novick D., H. Englemann, D. Wallach, O. Leitner, M. Revel and M. Rubinstein. Purification of soluble receptors from normal human urine by ligand‐affinity and immunoaffinity chromatography. J. Chromatogr. 510: 331–337, 1990.
 224. Oksenberg D., B. S. Dieckmann, and P. L. Greenberg. Functional interactions between colony‐stimulating factors and the insulin family hormones for human myeloid leukemic cells. Cancer Res. 50: 6471–6477, 1990.
 225. Opara, E. L., A. Laviano, M. M. Meguid, and Z. J. Yang. Correlation between food intake and CSF IL‐1 alpha in anorectic tumor bearing rats. Neuroreport 27: 750–752, 1995.
 226. Pahlman S., G. Meyerson, E. Lindgren, M. Schalling, and I. Johansson. Insulin‐like growth factor‐I shifts from promoting cell cell division to potentiating maturation during neuronal differentiation. Proc. Natl. Acad. Sci. U.S.A. 88: 9994–9998, 1991.
 227. Parnet P., S. Amindari, C. Wu, D. Brunke‐Reese, E. Goujon, J. A. Weyhenmeyer, R. Dantzer, and K. W. Kelley. Expression of type I and type II interleukin‐1 receptors in mouse brain. Mol. Brain Res. 27: 63–70, 1994.
 228. Parnet P., D. L. Brunke, E. Goujon, J. D. Mainard, A. Biragyn, S. Arkins, R. Dantzer, and K. W. Kelley. Molecular identification of two types of IL‐1 receptors in the murine pituitary gland J. Neuroendocrinal. 5: 213–219, 1993.
 229. Partanen J., T. P. Mäkela, R. Alitalo, H. Leshäslaiho, and K. Alitalo. Putative tyrosine kinases expressed in K‐562 human leukemia cells. Proc. Natl. Acad. Sci. U.S.A. 87: 8913–8917, 1990.
 230. Payne, L. C., F. Obal Jr., M. R. Opp, and J. M. Krueger. Stimulation and inhibition of growth hormone secretion by interleukin‐1 beta:the involvement of growth hormone releasing hormone. Neuroendocrinology 56: 118–123, 1992.
 231. Payne L. C., D. A. Weigent, and J. E. Blalock. Induction of pituitary sensitivity to interleukin‐1: a new function for corticotropin releasing hormone. Biochem. Biophys. Res. Comm. 198: 480–484, 1994.
 232. Peisen J. N., K. J. McDonnell, S. E. Mulroney, and M. D. Lumpkin. Endotoxin‐induced suppression of the somatotropic axis is mediated by interleukin‐1β and corticotropin‐releasing factor in the juvenille rat. Endocrinology 136: 3378–3390, 1995.
 233. Perlstein R. S., M. H. Whitnall, J. S. Abrams, E. H. Mougey, and R. Neta. Synergistic roles of interleukin‐6, interleukin‐1, and tumor necrosis factor in the adrenocorticotropin response to bacterial lipopolysaccharide in vivo. Endocrinology 132: 946–952, 1993.
 234. Phillips A. F., B. Persson, K. Hall, M. Lake, A. Skottner, T. Sanengen, and V. R. Sara. The effects of biosynthetic insulin‐like growth factor‐I supplementation on somatic growth, maturation, and erythropoiesis in the neonatal rat. Pediatr. Res. 23: 298–305, 1988.
 235. Plata‐Salamán, C. R. Meal patterns in response to the intracerebroventricular administration of interleukin‐1β in rats. Physiol. Behav. 55: 727–733, 1994.
 236. Plata‐Salamán, C. R., Y. Oomura, and Y. Kai. Tumor necrosis factor and interleukin‐1β: suppression of food intake by direct action in the central nervous system. Brain Res. 448: 106–114, 1988.
 237. Prickett M. D., A. M. Latimer, R. H. McCusker, G. J. Hausman, and A. K. Prestwood. Alterations of serum insulin‐like growth factor‐I (IGF‐I) and IGF‐binding proteins (IGFBPS) in swine infected with the protozoan parasite Sarcocystis Miescheriana. Dom. Anim. Endocrinol 9: 285–296, 1992.
 238. Probert L., J. Keffer, P. Carbella, H. Cazlaris, E. Patsavoudi, S. Stephens, E. Kaslaris, D. Kioussis, and G. Kollias. Wasting, ischemia, and lymphoid abnormalities in mice expressing T cell‐targeted human tumor necrosis factor transgenes. J. Immunol. 151: 1894–1906, 1993.
 239. Propes, M. J., and R. W. Johnson. Role of corticosterone in the behavioral effects of central interleukin‐1β. Physiol. Behav. 61: 7–13, 1997.
 240. Rainfray, M., B. Hamon‐Vilcot, X. Cnockaert, J. Pellerin, O. Bouillanne, D. Durand, and F. Piette. l'hormone de croissance chez l'adulte. Un elixir de jouvence? Therapie 50: 271–282, 1995.
 241. Ratajczak M. Z., W. I. Kuczynski, K. Onodera, J. Moore, J. Ratajczak, D. A. Kregenow, K. DeRiel, A. M. Gewirtz. A reappraisal of the role of insulin‐like growth factor I in the regulation of human hematopoiesis. J. Clin. Invest. 94: 320–327, 1994.
 242. Ratajczak, J, Q. Zhang, E. Pertusini, B. S. Wojczyk, M. A. Wasik, M. Z. Ratajczak. The role of insulin (INS) and insulinlike growth factor‐I (IGF‐I) in regulating human erythropoiesis. Studies in vitro under serum‐free conditions—comparison to other cytokines and growth factors. Leukemia 12: 371–381, 1998.
 243. Reiss K., P. Porcu, C. Sell, Z. Pietrzkowski, and R. Baserga. The insulin‐like growth factor‐I receptor is required for proliferation of hemopoietic cells. Oncogene 7: 2443–2448, 1992.
 244. Renno T., M. Krakowski, C. Piccirillo, J.‐Y. Lin, and T. Owens. TNF‐α expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis. J. Immunology 154: 944–953, 1995.
 245. Resnicoff M., D. Abraham, Y. Yutanawiboonchai, H. L. Rotman, J. Kajstura, R. Rubin, P. Zoltick, and R. Baserga. The insulin‐like growth factor I receptor protects tumor cells from apoptosis in vivo. Cancer Res. 55: 2463–2469, 1995.
 246. Rivier C., R. Chizzonite, and W. Vale. In the mouse, the activation of the hypothalamic‐pituitary‐adrenal axis by a lipo‐polysaccharide (endotoxin) is mediated through interleukin‐1. Endocrinology 125: 2800–2805, 1989.
 247. Rivier C., W. Vale, and M. Brown. In the rat, interleukin‐1α and ‐β stimulate adrenocorticotropin and catecholamine release. Endocrinology 125: 3096–3102, 1989.
 248. Robbins K., S. McCabe, T. Scheiner, J. Strasser, R. Clark, and P. Jardieu. Immunological effects of insulin‐like growth factor‐I‐enhancement of immunoglobulin synthesis. Clin. Exp. Immunol. 95: 337–342, 1994.
 249. Robert A., A. S. Olafsson, C. Lancaster, and W. Zhang. Interleukin‐1 is cytoprotective, antisecretory, stimulates PGE2 synthesis by the stomach and retards gastric emptying. Life Sci. 48: 123–134, 1991.
 250. Rodriguez‐Tarduchy, G., M.K.L. Collins, I. Garcia, and A. Lopez‐Rivas. Insulin‐like growth factor‐I inhibits apoptosis in IL‐3 dependent hemopoietic cells. J. Immunol. 149: 535–540, 1992.
 251. Rothwell, N. J. Annual review prize lecture: Cytokines‐killers in the brain? J. Physiol (Lond) 514: 3–17, 1999.
 252. Rudman D., A. G. Feller, H. S. Nagraf, G. A. Gergans, P. Y. Lalitha, A. F. Golberg, R. A. Schlenker, L. Cohn, and I. W. Rudman. Effects of human growth hormone in men over 60 years old. N. Engl. J. Med. 323: 1–6, 1990.
 253. Salmon, W. D., and W. H. Daughaday. A hormonally controlled serum factor which stimulates sulphate incorporation by cartilage in vitro. J. Lab. Clin. Med. 49: 825–836, 1957.
 254. Sanders M., S. Sorba, and N. Dainiak. Insulin‐like growth factors stimulate erythropoiesis in serum‐substituted umbilical cord blood cultures. Exp. Hematol. 21: 25–30, 1993.
 255. Saperas E. S., H. Yang, C. Rivier, and Y. Taché. Central action of interleukin‐1 to inhibit acid secretion in rats. Gastroenterology 99: 1599–1606, 1990
 256. Ref. no. Deleted.
 257. Sarraf, P., R. A. Frederich, E. M. Turner, G. Ma, N. T. Jaskowiak, D. J. Rivet, III, J. S. Flier, B. B. Lowell, D. L. Fraker, and H. R. Alexander. Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. J. Exp. Med. 185: 171–175, 1996.
 258. Sartin, J. L., T. H. Elsasser, D. R. Gunter, C. D. McMahon. Endocrine modulation of physiological responses to catabolic disease. Domest. Anim. Endocrinol. 15: 423–429, 1998.
 259. Sato, N., and A. Miyajima. Multimeric cytokine receptors: common versus specific functions. Curr. Opin. Cell Biol. 6: 174–179, 1994.
 260. Schacher, D. H., R. W. VanHoy, Q. Liu, S. Arkins, R. Dantzer, G. G. Freund, K. W. Kelley. Developmental expression of insulin receptor substrate‐2 during dimethylsulfoxide‐induced differentiation of human HL‐60 cells. J. Immunol. 164: 113–120, 2000.
 261. Scheven, B. A. A. and N. J. Hamilton. Stimulation of macrophage growth and multinucleated cell formation in rat bone marrow cultures by insulin‐like growth factor. Biochem. Bioph. Res. Comm. 174: 647–653, 1991.
 262. Schöbitz, B., E. R. deKloet, W. Sutano, and F. Holsboer. Cellular localization of interleukin‐6 mRNA and interleukin‐6 receptor mRNA in rat brain. Eur. J. Neurosci. 5: 1426–1435, 1993.
 263. Schöbitz, B., G. Pezeshki, T. Pohl, U. Hemmann, P. C. Heinrich, F. Holsboer, and J. M.H.M. Reul. Soluble interleukin‐6 (IL‐6) receptor augments central effects of IL‐6 in vivo. FASEB J 9: 659–664, 1995.
 264. Schwartz G. N., W. R. Hudgins, and J. F. Perdue. Glycosylated insulin‐like growth factor‐II promoted expansion of granulocyte‐macrophage colony‐formong cells in serum‐deprived liquid cultures of human peripheral blood cells. Exp. Hematol. 21: 1447–1454, 1993.
 265. Sharp A., T. Kukulansky, and A. Globerson. In vitro analysis of age‐related changes in the developmental potential of bone marrow thymocyte progenitors. Eur. J. Immunol. 20: 2541–2546, 1990.
 266. Silva, C. M., L. Hsienwe, M. J. Weber, M. O. Thorner. Differential tyrosine phosphorylation of JAK1, JAK2, and STAT1 by growth hormone and interferon‐γ in IM‐9 cells. J. Biol. Chem. 269: 27532–27539, 1994).
 267. Sims J. E., C. J. March, D. Cosman, M. B. Widmer, H. Robson MacDonald, C. J. McMahan, C. E. Grubin, J. M. Wignall, J. L. Jackson, S. M. Call, D. Friend, A. R. Alpert, S. Gillis, D. L. Urdal, and S. K. Dower. DNA expression cloning of the IL‐1 receptor, a member of the immunoglobulin superfamily. Science 241: 585–589, 1988.
 268. Sipe, K. J, R. Dantzer, K. W. Kelley, J. A. Weyhenmeyer. Expression of the 75 kDA TNF receptor and its role in contact‐mediated neuronal cell death. Brain Res. Mol. Brain Res. 62: 111–121, 1998.
 269. Sipe, K. S., D. Srisawasdi, R. Dantzer, K. W. Kelley, and J. A. Weyhenmeyer. An endogenous 55 kDa TNF receptor mediates cell death in a neural cell line. Brain Res. Mol. Brain Res. 38: 222–232, 1996.
 270. Sipponen P., S. Simila, Y. Collan, T. Autere, and R. Herva. Familial syndrome with panhypopituitarism, hypoplasia of the hypophysis, and poorly developed sella turcica. Archiv. Dis. Child. 53: 664–667, 1978
 271. Skottner A., R. G. Clark, L. Fryklund, and I. Robinson. Growth responses in a mutant dwarf rat to human growth hormone and recombinant human insulin‐like growth factor‐I. Endocrinology 124: 2519–2526, 1989.
 272. Smith B. B., and W. C. Wagner. Suppression of prolactin in pigs by Escherichia coli endotoxin. Science 224: 605–607, 1984.
 273. Smith P. E. Effect of hypophysectomy upon the involution of the thymus in the rat. Anat. Rec. 47: 119–129, 1930.
 274. Sortino, M. A. and P. L. Canonico. Neuroprotective effects of insulin‐like growth factor‐I in immortalized hypothalamic cells. Endocrinology 137: 1418–1422, 1996.
 275. Sotiropoulos, A., S. Moutoussamy, N. Binart, P. A. Kelly and J. Finidori. The membrane proximal region of the cytoplasmic domain of the growth hormone receptor is involved in the activation of Stat 3. FEES Lett. 369: 169–172, 1995)
 276. Spangelo, B. L., A. M. Judd, G. B. Call, J. Zumwalt, W. C. Gorospe. Role of the cytokines in the hypothalamic‐pituitary‐adrenal and gonadal axes. Neuroimmunomodulation 2: 299–312, 1995.
 277. Spitzer I. I., G. J. Bagby, K. Meszaros, and C. H. Lang. Altered control of carbohydrate metabolism in endotoxemia. Prog. Clin. Biol. Res. 286: 145–165, 1989.
 278. Stith R. D., and L. A. Templer. Peripheral endocrine and metabolic responses to centrally administered interleukin‐1. Neuroendocrinology 60, 215–224.
 279. Sugita, T., T. Totsuka, M. Saito, K. Yamiski, T. Taga, T. Hirano, and K. Kishimoto. Functional murine interleukin‐6 receptor with the intracisternal A particle gene product at its cytoplasmic domain: Its possible role in plasmacytomagenesis. J. Exp. Med. 171: 2001–2009, 1990.
 280. Taché, Y., and E. Saperas. Central actions of interleukin‐1 on gastrointestinal function. In: Neurobiology of Cytokines, Part B. edited by E. B. DeSouza, New York: Academic Press, 1993, p 169–184.
 281. Takao T., S. G. Culp, R. C. Newton, and E. B. De Souza. Type I interleukin‐1 receptors in the mouse brain‐endocrine‐immune axis labelled with [125I]recombinant human interleukin‐1 receptor antagonist. J. Neuroimmunol. 41: 51–60, 1992.
 282. Takao T., D. E. Tracey, and E. B. De Souza. Interleukin‐1 receptors in mouse brain: characterization and autoradiographic localization. Endocrinology 127: 3070–3078, 1990.
 283. Tamemoto H., T. Kadowaki, K. Tobe, T. Yagi, H. Sakura, T. Hayakawa, Y. Terauchi, K. Ueki, Y. Kaburagi, S. Satoh, H. Sekihara, S. Yoshloka, H. Horikoshi, Y. Furuta, Y. Ikawa, M. Kasuga, Y. Yazaki, and S. Aizawa. Insulin resistance and growth retardation in mice lacking insulin receptor substrate‐1. Nature 372: 182–186, 1994.
 284. Tapson V. F., M. Boni‐Schnetzler, P. F. Pilch, D. M. Center, and J. S. Berman. Structural and functional characterization of the human T lymphocyte receptor for insulin‐like growth factor I in vitro. J. Clin. Invest. 82: 950–957, 1988.
 285. Taub D. D., G. Tsarfaty, A. R. Lloyd, S. K. Durum, D. L. Longo, and W. J. Murphy. Growth hormone promotes human T cell adhesion and migration to both human and murine matrix proteins in vitro and directly promotes xenogeneic engraftment. J. Clin. Invest. 94: 293–300, 1994.
 286. Tchelingerian, J.‐L., J. Quinonero, J. Booss, and C. Jacque. Localization of TNFα and IL‐1α immunoreactivities in striatal neurons after surgical injury to the hippocampus. Neuron 10: 213–224, 1993.
 287. Terao A., M. Oikawa, and M. Saito. Tissue‐specific increase in norepinephrine turnover by central interleukin‐1, but not by interleukin‐6, in rats. Am. J. Physiol. 266 (Regulatory Integrative Comp. Physiol. 35): R400–R404, 1994.
 288. Tilders, F.J.H., R. H. DeRijk, A. M. van Dam, V.A.M. Vincent, K. Schotanus, and J.H.A. Persoons. Activation of the hypothalamus‐pituitary‐adrenal axis by bacterial endotoxins: routes and intermediate signals. Psychoneuroendocrinology 19: 209–232, 1994.
 289. Timsit J., W. Savino, B. Safieh, P. Chanson, M.‐C. Gagnerault, J.‐F. Bach, and M. Dardenne. Growth hormone and insulin‐like growth factor‐I stimulate hormonal function and proliferation of thymic epithelial cells. J. Clin. Endocrinol. Metab. 75: 183–188, 1992.
 290. Tingsborg S., M. Zetterström, K. Alheim, H. Hasanvan, M. Schultzberg, and T. Bartfai. Regionally specific induction of ICE mRNA and enzyme activity in the rat brain and adrenal gland by LPS. Brain Res. 712: 153–158, 1996.
 291. Tracey K. J., S. Morgello, B. Koplin, T. J. Fahey III, J. Fox, A. Aledo, K. R. Manogue and A. Cerami. Metabolic effect of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor‐secreting tumor in skeletal muscle induces cachexia while implantation in the brain induces predominantly acute anorexia. J. Clin. Invest. 86: 2014–2024, 1990.
 292. Tsujinaka T., J. Fujita, C. Ebisui, M. Yano, E. Kominami, K. Suzuki, K. Tanaka, A. Katsume, Y. Ohsugi, H. Shiozaki and M. Monden. Interleukin‐6 receptor antibody inhibits muscle atrophy and modulates proteolytic systems in interleukin 6 transgenic mice. J. Clin. Invest. 97: 244–249, 1996.
 293. Turnbull, A. V., and C. L. Rivier. Regulation of the hypothalamic‐pituitary‐adrenal axis by cytokines: actions and mechanisms of action. Physiol. Rev. 79: 1–71, 1999.
 294. Underwood, L. E. Growth hormone treatment, acromegaly, and relationship to cancer and leukemia. In: Growth Hormone II, edited by B. B. Bereu and R. F. Walker. New York: Springer‐Verlag, 1993, p 259–268.
 295. Vallieres, L., and S. Rivest. Interleukin‐6 is a needed proinflammatory cytokine in the prolonged neural activity and transcriptional activation of corticotropin‐releasing factor during endotoxemia. Endocrinology 140: 3890–3903, 1999.
 296. van Dam, A. M., S. Poole, M. Schultzberg, F. Zavala, and F. J. Tilders. Effects of peripheral administration of LPS on the expression of immunoreactive interleukin‐1 alpha, beta, and receptor antagonist in rat brain. Ann. NY Acad. Sci. 840: 128–138, 1998.
 297. van der Meer, M.J.M., C.G.J. Sweep, G. J. Pesman, G. F. Borm, and A.R.M.M. Hermus. Synergism between IL‐1β and TNF‐α on the activity of the pituitary‐adrenal axis and on food intake of rats. Am. J. Physiol. 268 (Endocrinol. Metab. 31): E551–E557, 1995.
 298. Velkeniers, B., P. Vergani, J. D'Haens, J. Trouillas, R. Hooghe, and E. L. Hooghe‐Peters. The expression of interleukin‐6 (IL‐6) and IL‐6 receptor (IL‐6‐R) mRNA in normal rat and human pituitary and in human pituitary adenomas. J. Histochem. Cytochem. 42: 67–76, 1993.
 299. Venters, H. D., R. Dantzer, G. G. Freund, and K. W. Kelley. Growth hormone and insulin‐like growth factor as cytokines in the immune system. In: Psychoneuroimmunology, Third Edition, edited by R. Ader, D. L. Feiten, and N. Cohen. New York: Academic Press, 2000 (in press).
 300. Venters, H. D., R. Dantzer, and K. W. Kelley. A new concept in neurodegeneration: TNF‐α is a silencer of survival signals. Trends Neurosci. 23: 175–180, 2000.
 301. Venters, H. D., Q. Tang, Q. Liu, R. W. VanHoy, R. Dantzer, and K. W. Kelley. A new mechanism of neurodegeneration: A proinflammatory cytokine inhibits receptor signaling by a survival peptide. Proc. Natl. Acad. Sci. U.S.A. 96: 9879–9884, 1999.
 302. Vriend C. Y., L. Zuo, D. G. Dyck, D. M. Nance, and A. H. Greenberg. Central administration of interleukin‐1β increases norepinephrine turnover in the spleen. Brain Res. Bull. 31: 39–42, 1993.
 303. Wada, Y., M. Sato, M. Niimi, M. Tamaki, T. Ishida, and J. Takahara. Inhibitory effects of interleukin‐1 on growth hormone secretion in conscious male rats. Endocrinology 136: 3936–3941, 1995.
 304. Wang, L.‐M., M. G. Myers, X.‐J. Sun, S. A. Aaronson, M. White and J. H. Pierce. IRS‐1: essential for IL‐4 stimulated mitogenesis in hematopoietic cells. Science 261: 1591–1594, 1993.
 305. Ref. no. Deleted.
 306. Warwick‐Davies, J., D. B. Lowrie, and P. J. Cole. Growth hormone is a human macrophage activating factor. Priming of human monocytes for enhanced release of H2O2. J. Immunol. 154: 1909–1918, 1995.
 307. Watkins L. R., S. F. Maier. Implications of immune‐to‐brain communication for sickness and pain. Proc. Natl. Acad. Sci. U.S.A. 96: 7710–713, 1999.
 308. Watkins L. R., S. F. Maier, and L. E. Goehler. Cytokine‐to‐brain communication: a review of analysis of alternative mechanisms. Life Sci. 57: 1011–1026, 1995.
 309. Watkins L. R., E. P. Wiertelak, L. E. Goehler, K. Mooney‐Heiberger, J. Martinez, L. Furness, K. P. Smith and S. F. Maier. Neurocircuitry of illness‐induced hyperalgesia. Brain Res. 639: 283–299, 1994.
 310. Watkins L. R., E. P. Wiertelak, L. E. Goehler, K. P. Smith, D. Martin, and S. F. Maier. Characterization of cytokine‐induced hyperalgesia. Brain Res. 654: 15–26, 1994.
 311. Weigent, D. A., and J. E. Blalock. Growth hormone and the immune system. Prog. NeuroEndocrinImmunol. 3: 321–324, 1994.
 312. Weigent D. A., and J. E. Blalock. Associations between the neuroendocrine and immune systems. J. Leukoc. Biol. 57: 137–150, 1995.
 313. Weigent, D. A., and J. E. Blalock. Production of peptide hormones and neurotransmitters by the immune system. Chem. Immunol. 69: 1–30, 1997.
 314. Weigent D. A., J. E. Blalock, and R. D. LeBoeuf. An antisense oligodeoxynucleotide to growth hormone messenger ribonucleic acid inhibits lymphocyte proliferation. Endocrinology 128: 2053–2057, 1991.
 315. Weingarten H. P. Cytokines and food intake: the relevance of the immune system to the student of ingestive behavior. Neurosci. Biobehav. Rev. 20: 163–170, 1995.
 316. Werner H., and D. LeRoith. Insulin‐like growth factor I receptor: structure, signal transduction and function. Diabetes Review 3: 28–37.
 317. Wexler B. C., A. E. Dolgin, and E. W. Tryczynski. Effects of bacterial polysaccharide (piromen) on the pituitary‐adrenal axis: adrenal ascorbic acid, cholesterol and histologic alterations. Endocrinology 61: 300–308, 1957a.
 318. Wexler B. C., A. E. Dolgin, and E. W. Tryczynski. Effects of bacterial polysaccharide (piromen) on the pituitary‐adrenal axis: further aspects of hypophyseal‐mediated control of response. Endocrinology 61: 488–499, 1957b.
 319. White, M. F. and C. R. Kahn. The insulin signaling system. J. Biol. Chem. 269: 1–4, 1994.
 320. White M. F., R. Maron, and C. R. Kahn. Insulin rapidly stimulates tyrosine phosphorylation of a Mr‐185,000 protein in intact cells. Nature. 318: 183–186, 1985.
 321. Wiedermann C. J., M. Niedermuhlbichler, D. Geissler, H. Beimpold, H. Braunsteiner. Priming of normal human neutrophils by recombinant human growth hormone. Br. J. Haematol. 78: 19–22, 1991.
 322. Williams G. T., C. A. Smith, E. Spooncer, T. M. Dexter, and D. R. Taylor. Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis. Nature 343: 76–79, 1990.
 323. Winston, L. A., and L. T. Hunter. JAK2, Ras ans Raf are required for activation of extracellular signal‐related kinase/mitogen‐activated protein kinase by growth hormone. J. Biol. Chem. 270: 30837–30840, 1995.
 324. Woloski B. M., E. M. Smith, W. J. Meyer, G. M. Fuller, and J. E. Blalock. Corticotropin‐releasing activity of monokines. Science 230: 1035–1037, 1985.
 325. Xu, B. C., X. Wang, C. James, and J. J. Kopchick. Characterization of growth hormone‐induced tyrosine‐phosphorylated proteins in mouse cells that express GH receptors. Receptor 5: 105–116, 1995.
 326. Yang Z. J., M. Koskeki, M. M. Meguid, J. R. Gleason, and D. Debonis. Synergistic effect of rhTNF‐α and rhIL‐1α in inducing anorexia in rats. Am. J. Physiol. 267 (Regulatory Integrative Comp. Physiol. 36): R1056–R1064, 1994.
 327. Yao, J. H., S. M. Ye, W. Burgess, J. F. Zachary, K. W. Kelley, and R. W. Johnson. Mice deficient in interleukin‐1beta converting enzyme resist anorexia induced by central lipopolysaccharide. Am. J. Physiol. 277 (Regulatory Integrative Comp. Physiol. 46): R1435–1443, 1999.
 328. Zamir O., P. O. Hasselgren, D. Allmen, and J. E. Fischer. In vivo administration of interleukin‐1α induces muscle proteolysis in normal and adrenalectomized rats. Metabolism 42: 204–208, 1993.
 329. Zamir O., P. O. Hasselgren, S. L. Kunkel, J. Frederick, T. Higashiguchi, and J. E. Fischer. Evidence that tumor necrosis factor participates in the regulation of muscle proteolysis during sepsis. Arch. Surg. 127: 170–174, 1992.

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Sean Arkins, Rodney W. Johnson, Christian Minshall, Robert Dantzer, Keith W. Kelley. Immunophysiology: The Interaction of Hormones, Lymphohemopoietic Cytokines, and the Neuroimmune Axis. Compr Physiol 2011, Supplement 23: Handbook of Physiology, The Endocrine System, Coping with the Environment: Neural and Endocrine Mechanisms: 469-495. First published in print 2001. doi: 10.1002/cphy.cp070421