Interactions Between the Nervous System and the Immune SystemImplications for Psychopharmacology
Adrian J. Dunn
Department of Pharmacology and Therapeutics
Louisiana State University Medical Center
Shreveport, Louisiana 71130.
1. Ader R, Cohen N. Psychoneuroimmunology: conditioning and stress. Annu Rev Psychol 1993;44:5385.
2. Ader R, Felten DL, Cohen N. Psychoneuroimmunology. 2nd ed. San Diego: Academic Press; 1991.
3. Banks WA, Ortiz L, Plotkin SR, Kastin AJ. Human interleukin (IL)1a, murine IL-1a and murine IL-1b are transported from blood to brain in the mouse by a shared saturable mechanism. J Pharmacol Exp Therapeut 1991;259:9881007.
4. Ben-Eliyahu S, Page GG. In vivo assessment of natural killer cell activity in rats. Prog NeuroEndocrinImmunol 1992;5:199214.
5. Bernton EW, Bryant HU, Holaday JW. Prolactin and immune function. In: Ader R, Felten DL, Cohen N, eds. Psychoneuroimmunology. 2nd ed. San Diego: Academic Press; 1991:403428.
6. Besedovsky HO, del Rey A, Sorkin E, Dinarello CA. Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones. Science 1986;233:652654.
7. Blalock JE, Smith EM. A complete regulatory loop between the immune and neuroendocrine systems. Fed Proc 1985;44:108111.
8. Bonneau RH, Sheridan JF, Feng NG, Glaser R. Stress-induced modulation of the primary cellular immune response to herpes simplex virus infection is mediated by both adrenal-dependent and independent mechanisms. J Neuroimmunol 1993;42:167176.
9. Caldwell CL, Irwin M, Lohr J. Reduced natural killer cell cytotoxicity in depression but not in schizophrenia. Biol Psychiatry 1991;30:11311138.
10. Carr DJJ. The role of endogenous opioids and their receptors in the immune system. Proc Soc Exp Biol Med 1991;198:710720.
11. Carr DJJ, Blalock JE. Neuropeptide hormones and receptors common to the immune and neuroendocrine systems: bidirectional pathway of intersystem communication. In: Ader R, Felten DL, Cohen N, eds. Psychoneuroimmunology. 2nd ed. San Diego: Academic Press; 1991:573588.
12. Chuluyan H, Saphier D, Rohn W, Dunn AJ. Noradrenergic innervation of the hypothalamus participates in the adrenocortical responses to interleukin-1. Neuroendocrinology 1992;56:106111.
13. Claman HN. How corticosteroids work. J Allergy Clin Immunol 1975;55:145151.
14. Coceani F, Lees J, Dinarello CA. Occurrence of interleukin-1 in cerebrospinal fluid of the conscious cat. Brain Res 1988;446:245250.
15. Crnic LS, Segall MA. Behavioral effects of mouse interferon-a and interferon-g and human interferon-a in mice. Brain Res 1992; 590:277284.
16. Cunnick JE, Lysle DT, Kucinski BJ, Rabin BS. Evidence that shock-induced immune suppression is mediated by adrenal hormones and peripheral b-adrenergic receptors. Pharmacol Biochem Behav 1990;36:645651.
17. Demitrack MA, Dale JK, Straus SE, et al. Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J Clin Endocrinol Metab 1991;73:12241234.
18. Dinarello CA. Interleukin-1 and its related cytokines. In: Sorg C, ed. Macrophage-Derived Cell Regulatory Factors: Cytokines. Basel: Karger; 1989:105150.
19. Dunn AJ. Systemic interleukin-1 administration stimulates hypothalamic norepinephrine metabolism parallelling the increased plasma corticosterone. Life Sci 1988;43:429435.
20. Dunn AJ. Psychoneuroimmunology for the psychoneuroendocrinologist: a review of animal studies of nervous system-immune system interactions. Psychoneuroendocrinology 1989;14:251274.
21. Dunn AJ. Interleukin-1 as a stimulator of hormone secretion. Prog NeuroEndocrinImmunol 1990;3:2634.
22. Dunn AJ. Endotoxin-induced activation of cerebral catecholamine and serotonin metabolism: comparison with interleukin-1. J Pharmacol Exp Therapeut 1992;261:964969.
23. Dunn AJ. The role of interleukin-1 and tumor necrosis factor a in the neurochemical and neuroendocrine responses to endotoxin. Brain Res Bull 1992;29:807812.
24. Dunn AJ. Role of cytokines in infection-induced stress. Ann NY Acad Sci 1993;697:189202.
25. Dunn AJ, Antoon M, Chapman Y. Reduction of exploratory behavior by intraperitoneal injection of interleukin-1 involves brain corticotropin-releasing factor. Brain Res Bull 1991;26:539542.
26. Dunn AJ, Powell ML, Moreshead WV, Gaskin JM, Hall NR. Effects of Newcastle disease virus administration to mice on the metabolism of cerebral biogenic amines, plasma corticosterone, and lymphocyte proliferation. Brain Behav Immun 1987;1:216230.
27. Dunn AJ, Welch J. Stress- and endotoxin-induced increases in brain tryptophan and serotonin metabolism depend on sympathetic nervous system activation. J Neurochem 1991;57:16151622.
28. Felten SY, Felten DL. Innervation of lymphoid tissue. In: Ader R, Felten DL, Cohen N, eds. Psychoneuroimmunology. 2nd ed. San Diego: Academic Press, 1991;2761.
29. Fontana A, Weber E, Dayer JM. Synthesis of interleukin 1/endogenous pyrogen in the brain of endotoxin-treated mice: a step in fever induction? J Immunol 1984;133:16961698.
30. Friedman RM, Vogel SN. Interferon with special emphasis on the immune system. Adv Immunol 1983;34:97140.
31. Fuchs D, Forsman A, Hagberg L, et al. Immune activation and decreased tryptophan in patients with HIV-1 infection. J Interferon Res 1990;10:599603.
32. Giulian D, Baker TJ, Shih L-CN, Lachman LB. Interleukin-1 of the central nervous system is produced by ameboid microglia. J Exp Med 1986;164:594604.
33. Giulian D, Lachman LB. Interleukin-1 stimulation of astroglial proliferation after brain injury. Science 1985;228:497499.
34. Goetzl EJ, Turck CW, Speedharan SP. Production and recognition of neuropeptides by cells of the immune system. In: Ader R, Felten DL, Cohen N, eds. Psychoneuroimmunology. 2nd ed. San Diego: Academic Press, 1991;263282.
35. Hadden JW, Hadden EM, Middleton E. Lymphocyte blast transformation1. Demonstration of adrenergic receptors in human peripheral lymphocytes. Cell Immunol 1970;1:583595.
36. Haour F, Ban E, Marquette C, Milon G, Fillion G. Brain interleukin-1 receptors: mapping, characterization and modulation. In: Rothwell NJ, Dantzer RD, eds. Interleukin-1 in the Brain. Oxford: Pergamon Press; 1992:1325.
37. Hart BL. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev 1988;12:123137.
38. Heijnen CJ, Kavelaars A, Ballieux RE. Corticotropin-releasing hormone and proopiomelanocortin-derived peptides in the modulation of immune function. In: Ader R, Felten DL, Cohen N, eds. Psychoneuroimmunology. 2nd ed. San Diego: Academic Press; 1991:429446.
39. Heyes MP. Relationship between interferon-g, indoleamine-2,3-dioxygenase and tryptophan. FASEB J 1991;5:30033004.
40. Heyes MP, Quearry BJ, Markey SP. Systemic endotoxin increases L-tryptophan, 5-hydroxyindoleacetic acid, 3-hydroxykynurenine and quinolinic acid content of mouse cerebral cortex. Brain Res 1989;491:173179.
41. Heyes MP, Saito K, Crowley JS, et al. Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. Brain 1992;115:12491273.
42. Higgins GA, Olschowka JA. Induction of interleukin-1b mRNA in adult rat brain. Molec Brain Res 1991;9:143148.
43. Irwin J, Livnat S. Behavioral influences on the immune system: stress and conditioning. Prog Neuro-Psychopharmacol Biol Psychiatry 1987;11:137143.
44. Irwin M, Hauger RL, Jones L, Provencio M, Britton KT. Sympathetic nervous system mediates central corticotropin releasing factor induced suppression of natural killer cytotoxicity. J Pharmacol Exp Ther 1990;255:101107.
45. Irwin M, Patterson T, Smith TL, et al. Reduction of immune function in life stress and depression. Biol Psychiatry 1990;27:2230.
46. Irwin M, Vale W, Rivier C. Central corticotropin-releasing factor mediates the suppressive effect of stress on natural killer cytotoxicity. Endocrinology 1990;126:28372844.
47. Jefferies WM. Cortisol and immunity. Med Hypoth 1991;34:198208.
48. Kent S, Bluthé R-M, Kelley KW, Dantzer R. Sickness behavior as a new target for drug development. TIPS 1992;13:2428.
49. Kiecolt-Glaser JK, Glaser R. Stress and immune function in humans. In: Ader R, Felten DL, Cohen N, eds. Psychoneuroimmunology. 2nd ed. San Diego: Academic Press; 1991;849867.
50. King DJ, Cooper SJ. Viruses, immunity and mental disorder. Brit J Psychiatry 1989;154:17.
51. Komaki G, Arimura A, Koves K. Effect of intravenous injection of IL-1b on PGE2 levels in several brain areas as determined by microdialysis. Endocrinol Metab 1992;25:E246E251.
52. Leu S-JC, Singh VK. Stimulation of interleukin-6 production by corticotropin-releasing factor. Cell Immunol 1992;143:220227.
53. MacPhee IAM, Antoni FA, Mason DW. Spontaneous recovery of rats from experimental allergic encephalomyelitis is dependent on regulation of the immune system by endogenous adrenal corticosteroids. J Exp Med 1989;169:431445.
54. Madden KS, Livnat S. Catecholamine action and immunologic reactivity. In: Ader R, Felten DL, Cohen N, eds. Psychoneuroimmunology. 2nd ed. San Diego: Academic Press; 1991:283310.
55. Maier SF, Laudenslager ML. Inescapable shock, shock controllability and mitogen stimulated lymphocyte proliferation. Brain Behav Immun 1988;2:8791.
56. Matta SG, Linner KM, Sharp BM. Interleukin-1-a and interleukin-1-b stimulate adrenocorticotropin secretion in the rat through a similar hypothalamic receptors(s): effects of interleukin-1 receptor antagonist protein. Neuroendocrinology 1993;57:1422.
57. Matta SG, Singh J, Newton R, Sharp BM. The adrenocorticotropin response to interleukin-1b instilled into the rat median eminence depends on the local release of catecholamines. Endocrinology 1990;127:21752182.
58. Matta SG, Weatherbee J, Sharp BM. A central mechanism is involved in the secretion of ACTH in response to IL-6 in rats: comparison to and interaction with IL-1b. Neuroendocrinology 1992;56: 516525.
59. McCarthy DO, Kluger MJ, Vander AJ. Effect of centrally administered interleukin-1 and endotoxin on food intake of fasted rats. Physiol Behav 1986;36:745749.
60. McGillis JP, Mitsuhashi M, Payan DG. Immunologic properties of substance P. In: Ader R, Felten DL, Cohen N, eds. Psychoneuroimmunology. 2nd ed. San Diego: Academic Press; 1991:209223.
61. Meyers CA, Scheibel RS, Forman AD. Persistent neurotoxicity of systemically administered interferon-alpha. Neurology 1991;41: 672676.
62. Munck A, Guyre P. Glucocorticoid physiology, pharmacology and stress. Adv Exp Med Biol 1986;196:8196.
63. Murray RM, Jones P, O'Callaghan E, Takei N, Sham P. Genes, viruses and neurodevelopmental schizophrenia. J Psychiatr Res 1992;26:225235.
64. Nemeroff CB, Widerlöv E, Bissette G, et al. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 1984;226:13421344.
65. Opp MR, Kapas L, Toth LA. Cytokine involvement in the regulation of sleep. Proc Soc Exp Biol Med 1992;201:1627.
66. Ottaway CA. Vasoactive intestinal peptide and immune function. In: Ader R, Felten DL, Cohen N, eds. Psychoneuroimmunology. 2nd ed. San Diego: Academic Press, 1991;225262.
67. Otterness IG, Seymour PA, Golden HW, Reynolds JA, Daumy GO. The effects of continuous administration of murine interleukin-1a in the rat. Physiol Behav 1988;43:797804.
68. Renoux G, Biziere K. Neocortex lateralization of immune function and of the activities of imuthiol, a T-cell-specific immunopotentiator. In: Ader R, Felten DL, Cohen N, eds. Psychoneuroimmunology. 2nd ed. San Diego: Academic Press; 1991:127147.
69. Rivier C, Vale W, Brown M. In the rat, interleukin-1a and -b stimulate adrenocorticotropin and catecholamine release. Endocrinology 1989;125:30963102.
70. Roszman TL, Cross RJ, Brooks WH, Markesbery WR. Neuroimmunomodulation: effects of neural lesions on cellular immunity. In: Guillemin R, Cohn M, Melnechuk T, eds. Neural modulation of immunity. New York: Raven Press; 1985:95109.
71. Sanders VM, Munson AE. Norepinephrine and the antibody response. Pharmacol Rev 1985;37:229248.
72. Saphier D. Neurophysiological and endocrine consequences of immune activity. Psychoneuroendocrinology 1989;14:6387.
73. Schultzberg M. Location of interleukin-1 in the nervous system. In: Rothwell NJ, Dantzer RD, eds. Interleukin-1 in the brain. Oxford: Pergamon Press; 1992:111.
74. Selye H. The stress of my life. 2nd ed. New York: Van Nostrand Reinhold; 1979.
75. Shahabi NA, Peterson PK, Sharp BM. b-Endorphin binding to naloxone-insensitive sites on a human mononuclear cell line (U937): effects of cations and guanosine triphosphate. Endocrinology 1990;126:30063015.
76. Sharp B, Linner K. What do we know about the expression of proopiomelanocortin transcripts and related peptides in lymphoid tissue? Endocrinology 1993;133:19211922.
77. Shavit Y, Lewis JW, Terman GW, Gale RP, Liebeskind JC. Opioid peptides mediate the suppressive effect of stress on natural killer cell cytotoxicity. Science 1984;223:188190.
78. Spadaro F, Dunn AJ. Effects of neuropeptides on cells of the immune system. Clin Immun Newslett. 1991;11:105111.
79. Stein C, Hassan AHS, Przewlocki R, Gramsch C, Peter K, Herz A. Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation. Proc Natl Acad Sci USA 1990;87:59355939.
80. Stein M, Miller AH, Trestman RL. Depression and the immune system. In: Ader R, Felten DL, Cohen N, eds. Psychoneuroimmunology. 2nd ed. San Diego: Academic Press; 1991;897930.
81. Stenzel-Poore M, Vale WW, Rivier C. Relationship between antigen-induced immune stimulation and activation of the hypothalamic-pituitary-adrenal axis in the rat. Endocrinology 1993; 132:13131318.
82. Sternberg EM, Young WS, Bernardini R, et al. A central nervous system defect in biosynthesis of corticotropin-releasing hormone is associated with susceptibility to streptococcal cell wall-induced arthritis in Lewis rats. Proc Natl Acad Sci USA 1989;86:47714775.
83. Sundar SK, Cierpial MA, Kilts C, Ritchie JC, Weiss JM. Brain IL-1-induced immunosuppression occurs through activation of both pituitary-adrenal axis and sympathetic nervous system by corticotropin-releasing factor. J Neurosci 1990;10:37013706.
84. Takamoto T, Hori Y, Koga Y, Toshima H, Hara A, Yokoyama MM. Norepinephrine inhibits human natural killer cell activity in vitro. Int J Neurosci 1991;58:127131.
85. Takao T, Tracey DE, Mitchell WM, De Souza EB. Interleukin-1 receptors in mouse brain: characterization and neuronal localization. Endocrinology 1990;127:30703078.
86. Tchelingerian JL, Quinonero J, Booss J, Jacque C. Localization of TNFa and IL-1a immunoreactivities in striatal neurons after surgical injury to the hippocampus. Neuron 1993;10:213224.
87. Tsagarakis S, Gillies G, Rees LH, Besser M, Grossman A. Interleukin-1 directly stimulates the release of corticotrophin releasing factor from rat hypothalamus. Neuroendocrinology 1989; 49:98101.
88. Tsokos GC, Balow JE. Regulation of human cellular immune responses by glucocorticosteroids. In: Plotnikoff NP, Faith RE, Murgo AJ, Good RA, eds. Enkephalins and endorphins: stress and the immune system. New York: Plenum Press; 1986:159171.
89. Uehara A, Gottschall PE, Dahl RR, Arimura A. Interleukin-1 stimulates ACTH release by an indirect action which requires endogenous corticotropin releasing factor. Endocrinology 1987;121:15801582.
90. Weber RJ, Pert A. The periaqueductal gray matter mediates opiate-induced immunosuppression. Science 1989;245:188190.
91. Webster EL, Tracey DE, Jutila MA, Wolfe SA, De Souza EB. Corticotropin-releasing factor receptors in mouse spleen: identification of receptor-bearing cells as resident macrophages. Endocrinology 1990;127:440452.
92. Wood PG, Karol MH, Kusnecov AW, Rabin BS. Enhancement of antigen-specific humoral and cell-mediated immunity by electric footshock stress in rats. Brain Behav Immun 1993;7:121134.
93. Woodroofe MN, Sarna GS, Wadhwa M, et al. Detection of interleukin-1 and interleukin-6 in adult rat brain, following mechanical injury, by in vivo microdialysis: evidence of a role for microglia in cytokine production. J Neuroimmunol 1991;33:227236.
94. Zalcman S, Shanks N, Anisman H. Time-dependent variations of central norepinephrine and dopamine following antigen administration. Brain Res 1991;557:6976.
95. Zuckerman SH, Shellhaas J, Butler LD. Differential regulation of lipopolysaccharide-induced interleukin-1 and tumor necrosis factor synthesis: effects of endogenous and exogenous glucocorticoids and the role of the pituitary-adrenal axis. Eur J Immunol 1989;19:301305.
#1 The cytokines are a large group of proteins that were originally identified as products of immune cells that functioned as chemical messengers between cells of the immune system. They are now known to be synthesized by a variety of different cell types in the body and can have a very wide range of actions on many organ systems. The cytokines include the interleukins (of which there are at least 13), the interferons, tumor necrosis factors, and a variety of cell growth-stimulating factors.
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