Skip to main content

Advertisement

SpringerLink
Log in

The neuroendocrine-immune axis

  • Published:
Springer Seminars in Immunopathology Aims and scope Submit manuscript

Summary

The three different systems that contribute to development and maintenance of homeostasis, the nervous, endocrine and immune systems are closely interrelated. First, it was established that the neuroendocrine system was able to modulate the immune response. More recently, it has been shown that the immune system is able to function as a neuroendocrine organ, since it can synthesize not only hormones and neuropeptides, but also cytokines that have an impact on the neuroendocrine system. This has led to the demonstration of the existence of cytokine receptors within the nervous system. At the same time, various cytokine effects on the nervous system have been described including growth-promoting activity, neuromodulatory action, fever induction, sleep and decreased food intake. The latest element in this network of intricate interrelationships has been the demonstration of cytokine production by cells of the nervous system. Moreover, it appears that the brain is no longer the immunologically deprived site it was once thought to be, and that all phases of an immune response can potentially occur within the confines of the BBB.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Adachi N, Yamaguchi K, Miyake Y, Honda S, Nagasaki K, Akiyama Y, Adachi I, Abe K (1990) Parathyroid hormone-related protein is a possible autocrine growth inhibitor for lymphocytes. Biochem Biophys Res Commun 166:1088

    Google Scholar 

  2. Ader R, Cohen S (1981) Conditioned immunopharmacologic responses. In: Ader R (ed) Psychoneuroimmunology. Academic Press, New York pp 281–319

    Google Scholar 

  3. Ader R, Cohen S (1982) Behaviorally conditioned immunosuppression and murine systemic lupus erythematosus. Science 215:1534

    Google Scholar 

  4. Ameisen JC, Meade R, Askenase PW (1989) A new interpretation of the involvement of serotonin in delayed-type hypersensitivity. J Immunol 142:3171

    Google Scholar 

  5. Ansar Ahmed S, Penhale WJ, Talal N (1985) Sex hormones, immune responses, and autoimmune diseases. Am J Pathol 121:531

    Google Scholar 

  6. Ataya KM, Sakr W, Blacker CM, Mutchnick MG, Latif ZA (1989) Effect of Gn-RH agonists on the thymus in female rats. Acta Endocrinol (Copenh) 121:833

    Google Scholar 

  7. Audhya T, Jain R, Hollander CS (1991) Receptor-mediated immunomodulation by corticotropin-releasing factor. Cell Immunol 134:77

    Google Scholar 

  8. Bateman A, Singh A, Kral T, Solomon S (1989) The immune hypothalamic-pituitaryadrenal axis. Endocr Rev 10:92

    CAS  PubMed  Google Scholar 

  9. Benveniste EN (1988) Lymphokines and monokines in the neuroendocrine system. Prog Allergy 43:84

    Google Scholar 

  10. Bhatena SJ, Gazdar AF, Schechter GP, Russel EK, Soehnlen FE, Gritsman A, Recan L (1982) Expression of glucagon receptors on T-and B-lymphoblasts: comparison with insulin receptors. Endocrinology 111:684

    Google Scholar 

  11. Blalock JE (1988) Production of neuroendocrine peptide hormones by the immune system. Prog Allergy 43:1

    Google Scholar 

  12. Bockman DE, Kirby ML (1984) Dependence of thymus development on derivatives of the neural crest. Science 223:498

    Google Scholar 

  13. Body JJ, Glibert F, Nejai S, Fernandez G, van Langendonck A, Borkowski A (1990) Calcitonin receptors on circulating normal human lymphocytes. J Clin Endocrinol Metab 71:675

    Google Scholar 

  14. Bost KL (1988) Hormone and neuropeptide receptors on mononuclear leukocytes. Prog Allergy 43:68

    Google Scholar 

  15. Boukhris W, Kouassi E, Descotes J, Cordier G, Revillard JP (1987) Impaired T-dependent immune response in l-dopa-treated BALB/c mice. J Clin Lab Immunol 23:185

    Google Scholar 

  16. Bryant HU, Roudebush RE (1990) Suppressive effects of morphine pellet implants on in vivo parameters of immune functions. J Pharmacol Exp Ther 255:410

    Google Scholar 

  17. Burgess C (1987) Stress and cancer. Cancer Surv 6:403

    Google Scholar 

  18. Calder V, Owen S, Watson C, Feldmann M, Davison A (1989) MS: a localized immune disease of the central nervous system. Immunol Today 10:99

    Google Scholar 

  19. Cohen S, Williamson GM (1991) Stress and infectious disease in humans. Psychol Bull 109:5

    Google Scholar 

  20. Costa O, Boutet C, Sauvage P, Michel JP, Deschaux P (1990) Age-dependent LH and FSH effect on the proliferation of women's peripheral blood lymphocytes in vitro. Int J Immunopharmacol 12:821

    Google Scholar 

  21. Cowie DM, Parson JP, Raphael T (1924) Insulin and mental depression. Arch Neurol 12:522

    Google Scholar 

  22. Dantzer R, Kelley KW (1989) Stress and immunity: an integrated view of relationship between the brain and the immune system. Life Sci 44:1995

    Google Scholar 

  23. Dardenne M, Savino W (1990) Neuroendocrine control of the thymic epithelium: modulation of thymic endocrine function, cytokeratin expression and cell proliferation by hormones and neuropeptides. Prog Neuroendocrinoimmunol 3:18

    Google Scholar 

  24. Descotes J, Tedone R, Evreux JC (1985) Different effects of psychotropic drugs on delayed hypersensitivity responses in mice. J Neuroimmunol 9:81

    Google Scholar 

  25. Dhib-Jalbut S, McFarlin DE (1989) Macrophages, microglia and other presenting cells in neurological disorders. Prog Neuroendocrinoimmunol 2:86

    Google Scholar 

  26. Dorian B, Garfinkel PE (1987) Stress, immunity and illness: a review. Psychol Med 17:393

    Google Scholar 

  27. Eck HP, Frey H, Droge W (1989) Elevated plasma glutamate concentrations in HIV-1 infected patients may contribute to loss of macrophage and lymphocyte functions. Int Immunol 1:367

    Google Scholar 

  28. Fabris N, Muzzioli M, Mocchegiani E (1982) Recovery of age-dependent immunological deterioration in BALB/c mice by short-term treatment with l-thyroxine. Mech Ageing Dev 18:327

    Google Scholar 

  29. Felten DL, Felten SY, Carlson SL, Olschowka JA, Livnat S (1985) Noradrenergic and peptidergic innervation of lymphoid tissue. J Immunol 135:755s

    Google Scholar 

  30. Felten SY, Felten DL, Bellinger DL, Carlson SL, Ackerman KD, Madden KS, Olschowka JA, Livnat S (1988) Noradenergic sympathetic innervation of lymphoid organs. Prog Allergy 43:14

    Google Scholar 

  31. Fitzgerald L (1988) Exercise and the immune system. Immunol Today 9:337

    Google Scholar 

  32. Fitzmaurice MA (1988) Psychological relationships among stress, viruses, and cancer in experimental animals. Int J Neurosci 39:307

    Google Scholar 

  33. Fox BH (1983) Current theory of psychogenic effects on cancer incidence and prognosis. J Psychosoc Oncol 1:17

    Google Scholar 

  34. Fride E, Collins RL, Skolnick P, Arora PK (1990) Strain dependent association between immune function and paw preference in mice. Brain Res 522:246

    Google Scholar 

  35. Garau L, Memo M, Pizzi M, Missale C, Carai MAM, Boi W, Ennas MG, Manconi PE, Spano PF (1989) Properties of benzodiazepine binding sites in peripheral blood lymphocytes. J Clin Lab Anal 3:332

    Google Scholar 

  36. Geenen V, LeGros JJ, Franchimont P, Baudrihaye M, Defresne MP, Boniver J (1986) The neuroendocrine thymus: coexistence of oxytocin and neurophysin in the human thymus. 232:508

    Google Scholar 

  37. Geenen V, Robert F, Martens H, Fatemi M, Defresne MP, Boniver J, LeGros JJ, Franchimont P (1990) Cellular and molecular aspects of the neuroendocrine immune dialogue in T-cell differentiation. In: Müller EE, MacLeod RM (eds) Neuroendocrine perspectives vol. 8. Springer, New York, pp 77–92

    Google Scholar 

  38. Geppetti P, Maggi CA, Zecchi-Orlandini P, Santicioli A, Meli S, Frilli MG, Spillantini MG, Amenta F (1987) Substance P-like immunoreactivity in capsaicin sensitive structures of the thymus Regul Pept 18:321

    Google Scholar 

  39. Gilhus NE, Matre R, Aarli JA (1982) Lymphocyte subpopulations and lymphocyte function in phenytoin-treated patients with epilepsy. Int J Immunopharmacol 4:43

    Google Scholar 

  40. Glaser R, Kiecolt-Glaser J (1987) Stress-associated depression in cellular immunity: implications for acquired immune deficiency syndrome (AIDS). Brain Behav Immun 1:107

    Google Scholar 

  41. Griffin WST, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, White CL, Araoz C (1989) Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci USA 86:7611

    Google Scholar 

  42. Hafler DA, Weiner HL (1989) MS: a CNS and systemic autoimmune disease. Immunol Today 10:104

    Google Scholar 

  43. Hartung HP (1988) Activation of macrophages by neuropeptides. Brain Behav Immun 2:275

    Google Scholar 

  44. Homo-Delarche F, Duval D (1987) Glucocorticoid receptors in lymphoid tissue. In: Berczi E, Kovacs K, (eds) Hormones and immunity. MTP Press, Lancaster, pp 1–19

    Google Scholar 

  45. Homo-Delarche F, Fitzpatrick F, Christeff N, Nunez EA, Bach JF, Dardenne M (1991) Sex steroids, glucocorticoids, stress and autoimmunity, J Steroid Biochem 40:619

    Google Scholar 

  46. Jankovic BD (1989) Neuroimmunomodulation: facts and dilemnas. Immunol Lett 21:101

    Google Scholar 

  47. Jankovic BD, Isakovic K, Micic M, Knezevic R (1981) The embryonic lympho-neuro-endocrine relationship. Clin Immunol Immunopathol 18:108

    Google Scholar 

  48. Jemmott JB, Locke SE (1984) Psychosocial factors, immunologic mediation, and human susceptibility to infectious diseases: how much do we know? Psychol Bull 95:78

    Google Scholar 

  49. Jerrells TR, Marietta CA, Weight FF, Eckardt M (1990) Effect of adrenalectomy on ethanol-associated immunosuppression. Int J Immunopharmacol 12:435

    Google Scholar 

  50. Johnson HM, Torres BA (1988) Immunoregulatory properties of neuroendocrine peptide hormones. Prog Allergy 43:37

    Google Scholar 

  51. Jones JM, Yeralan O, Hines G, Maher M, Roberts DW, Benson RW (1990) Effects of lithium and rubidium on immune responses of rats. Toxicol Lett 52:163

    Google Scholar 

  52. Justice A (1985) Review of the aspects of stress on cancer in laboratory animals: importance of time of stress application and type of tumor. Psychol Bull 98:108

    Google Scholar 

  53. Khansari DN, Murgo AJ, Faith RE (1990) Effects of stress on the immune system. Immunol Today 11:170

    Google Scholar 

  54. Koenig JI (1991) Presence of cytokines in the hypothalamic-pituitary axis. Prog Neuroendocrinoimmunol 4:143

    Google Scholar 

  55. Leclere J, Weryha J (1989) Stress and autoimmune endocrine diseases. Horm Res 31:90

    Google Scholar 

  56. Le Douarin NM, Jotereau FV (1975) Tracing of cells of the avian thymus through embryonic life in interspecific chimeras. J Exp Med 142:17

    Google Scholar 

  57. Lignon MF, Bernad N, Martinez J (1991) Pharmacological characterization of type B cholecystokinin binding sites on the human Jurkat T lymphocyte cell line. Mol Pharmacol 39:615

    Google Scholar 

  58. Malec P, Zeman K, Markiewicz K, Tchorzewski H, Novak Z, Baj Z (1989) Short-term somatostatin infusion affects T lymphocyte responsiveness in humans. Immunopharmacology 17:45

    Google Scholar 

  59. Malone JD, Richards M, Kahn AJ (1986) Human peripheral monocytes express putative receptors for neuroexcitatory aminoacids. Proc Natl Acad Sci USA 83:3307

    Google Scholar 

  60. Manolagas SC, Hustmyer FG, Yu XP (1990) Immunomodulating properties of 1,25-dihydroxyvitamin D3. Kidney Int 38:S9

    Google Scholar 

  61. Martinez F, Coleman JW (1989) The effects of selected drugs, including chlorpromazine and nonsteroidal anti-inflammatory agents, on polyclonal IgG synthesis and interleukin 1 production by human peripheral blood mononuclear cells in vitro. Clin Exp Immunol 76:252

    Google Scholar 

  62. Maslinski W, Kullberg M, Nordstrom O, Bartfai T (1988) Muscarinic receptors and receptor-mediated actions on rat thymocytes. J Neuroimmunol 17:265

    Google Scholar 

  63. Mason D, MacPhee I, Antoni F (1990) The role of the neuroendocrine system in determining genetic susceptibility to experimental allergic encephalomyelitis in the rat. Immunology 70:1

    Google Scholar 

  64. Mufti SI, Prabhala R, Moriguchi S, Sipes G, Watson RR (1988) Functional and numerical alterations induced by ethanol in the cellular immune system. Immunopharmacology 15:85

    Google Scholar 

  65. Munck A, Guyre PM, Holbrook NJ (1984) Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 5:25

    Google Scholar 

  66. Neveu PJ (1988) Cerebral neocortex modulation of immune functions. Life Sci 42:1917

    Google Scholar 

  67. Neveu PJ, Le Moal M (1990) Physiological basis for neuroimmunomodulation. Fundam Clin Pharmacol 4:281

    Google Scholar 

  68. Nilsson G, Alving K, Ahlstedt S, Hokfelt T, Lundberg JM (1990) Peptidergic innervation of rat lymphoid tissue and lung: relation to mast cells and sensitivity to capsaicin and immunization. Cell Tissue Res 262:125

    Google Scholar 

  69. Nistico G, De Sarro G (1991) Is interleukin 2 a neuromodulator in the brain? Trends Neurosci 14:146

    Google Scholar 

  70. Nybroe O (1990) Structure and function of the neural cell adhesion NCAM and L1. Adv Exp Med Biol 265:185

    Google Scholar 

  71. Pert CB, Ruff MR, Hill JM (1988) AIDS as a neuropeptide disorder: peptide T, VIP and the HIV receptor. Psychopharmacol Bull 24:315

    Google Scholar 

  72. Plata-Salaman CR (1991) Immunoregulators in the nervous system. Neurosci Biobehav Rev 15:185

    Google Scholar 

  73. Plaut M (1987) Lymphocyte hormone receptors. Annu Rev Immunol 5:621

    Google Scholar 

  74. Rabin BS, Cohen S, Ganguli R, Lysle DT, Cunnick JE (1989) Bidirectional interaction between the central nervous system and the immune system. Crit Rev Immunol 9:279

    Google Scholar 

  75. Sacerdote P, Bianchi M, Panerai AE (1990) Human monocyte chemotactic activity of calcitonin and somatostatin-related peptides: modulation by chronic peptide treatment. J Clin Endocrinol Metab 70:141

    Google Scholar 

  76. Sakabe K, Seiki K, Fujii-Hanamoto H (1986) Histochemical localization of progestin receptor cells in the rat thymus. Thymus 8:97

    Google Scholar 

  77. Sanders WM, Munson AE (1985) Norepinephrine and the antibody response. Pharmacol Rev 37:229

    Google Scholar 

  78. Segal J, Ingbar SH (1982) Specific binding sites for triiodothyronine in the plasma membrane of rat thymocytes. Correlation with biochemical responses. J Clin Invest 70:919

    Google Scholar 

  79. Shaskan EG, Lovett EJ (1980) Effects of haloperidol, a dopamine receptor antagonist, on a delayed-type hypersensitivity reaction to 1-chloro, 2–4-dinitrobenzene in mice. Res Commun Psychol Psychiatry Behav 5:241

    Google Scholar 

  80. Smith EM (1988) Hormonal activities of lymphokines, monokines, and other cytokines. Prog Allergy 43:121

    Google Scholar 

  81. Soder O, Hellstrom PM (1987) Neuropeptide regulation of human thymocyte, guinea pig T lymphocyte and rat B lymphocyte mitogenesis. Int Arch Allergy Appl Immunol 84:205

    Google Scholar 

  82. Spanos NP, Stenstrom RJ, Johnston JC (1988) Hypnosis, placebo, and suggestion in the treatment of warts. Psychosom Med 50:245

    Google Scholar 

  83. Sreedharan SP, Kodama KT, Peterson KE, Goetzl EJ (1989) Distinct subsets of somatostatin receptors on cultured human lymphocytes. J Biol Chem 264:949

    Google Scholar 

  84. Stefano GB (1989) Role of opioid neuropeptides in immunoregulation. Prog Neurobiol 33:149

    Google Scholar 

  85. Stein M (1991) Depression, the immune system, and health and illness. Arch Gen Psychiatry 48:171

    Google Scholar 

  86. Stepien H, Pawlikowska A, Pawlikowska M (1988) Effects of benzodiazepines on thymus cell proliferation. Thymus 12:117

    Google Scholar 

  87. Sternberg EM, Hill JM, Chrousos GP, Kamilaris T, Listwak SJ, Gold PW, Wilder RL (1989) Inflammatory mediator-induced hypothalamic-pituitary-adrenal axis activation is defective in streptococcal cell wall arthritis-susceptible lewis rats. Proc Natl Acad Sci USA 86:2374

    Google Scholar 

  88. Sternberg EM, Young WS, Bernardini R, Calogero AE, Chrousos GP, Gold PW, Wilder RL (1989) A central nervous system defect in biosynthesis of corticotropin-releasing hormone in associated with susceptibility to streptococcal cell wall-induced arthritis in Lewis rats. Proc Natl Acad Sci USA 86:4771

    Google Scholar 

  89. Stimson WH (1987) Sex steroids, receptors and immunity. In: Berczi E, Kovacs K (eds) Hormones and immunity. MTP Press, Lancaster, pp 43–53

    Google Scholar 

  90. Stites DP, Siiteri PK (1983) Steroids as immunosuppressants in pregnancy. Immunol Rev 75:117

    Google Scholar 

  91. Takasu N, Komiya I, Nagasawa Y, Asawa T, Yamada T (1990) Exacerbation of autoimmune thyroid dysfunction after unilateral adrenalectomy in patients with Cushing's syndrome due to an adrenocortical adenoma. N Engl J Med 322:1708

    Google Scholar 

  92. Tecoma ES, Leighton YH (1985) Psychic distress and the immune response. Life Sci 36:1799

    Google Scholar 

  93. Thatcher N, Wan HH, Swindell R, Wilkinson PM, Crowther D (1982) Effects of diphenylhydantoin on killer cell activity and other immunological functions. Int J Immunopharmacol 4:167

    Google Scholar 

  94. Tiffany CW, Burch RM (1989) Bradykinin stimulates tumor necrosis factor and interleukin 1 release from macrophages. FEBS Lett 247:189

    Google Scholar 

  95. Umeda Y, Takamiya M, Ioshizaki H, Arisawa M (1988) Inhibition of mitogen-stimulated T lymphocyte proliferation by calcitonin gene-related peptide. Biochem Biophys Res Commun 154:227

    Google Scholar 

  96. Villemain F, Chatenoud L, Galinovski A, Homo-Delarche F, Ginestet D, Loo H, Zarifian E, Bach JF (1989) Aberrant T-cell mediated immunity in untreated schizophrenic patients: deficient interleukin 2 production. Am J Psychiatry 146:609

    Google Scholar 

  97. Watzl B, Watson RR (1990) Immunomodulation by cocaine: a neuroendocrine mediated response. Life Sci 46:1319

    Google Scholar 

  98. Webster EL, Tracey DE, Jutila MA, Wolfe SE, De Souza EB (1990) Corticotropin-releasing factor receptors in mouse spleen: identification of receptor-bearing cells as resident macrophages. Endocrinology 127:440

    Google Scholar 

  99. Weigent DA, Blalock JE (1987) Interactions between the neuroendocrine and immune systems: common hormones and receptors. Immunol Rev 100:79

    Google Scholar 

  100. Wekerle H, Linington C, Lassman H, Meyermann R (1986) Cellular immune reactivity within the CNS. Trends Neurosci 9:271

    Google Scholar 

  101. Westermann J, Pabst R (1990) Lymphocyte subsets in the blood: a diagnostic window of the lymphoid system? Immunol Today 11:406

    Google Scholar 

  102. Wong GHW, Bartlett PF, Clark-Lewis I, McKimm-Breschkin JL, Schrader JW (1985) Interferon-γ induces the expression of H-2 and Ia antigens on brain cells. J Neuroimmunol 7:255

    Google Scholar 

  103. Yaha MD, Watson RR (1987) Immunomodulation by morphine and marijuana. Life Sci 41:2503

    Google Scholar 

  104. Zavala F, Haumont J, Lenfant M (1984) Interaction of benzodiazepines with mouse macrophages. Eur J Pharmacol 106:561

    Google Scholar 

  105. Zavala F, Taupin V, Descamps-Latscha B (1990) In vivo treatment with benzodiazepines inhibits murine phagocyte oxidative metabolism and production of interleukin 1, tumor necrosis factor and interleukin 6. J Pharmacol Exp Ther 255:442

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. CNRS URA 1461, Hôpital Necker, 161, rue de Sèvres F-75730, 15, Paris Cedex, France

    Françoise Homo-Delarche & Mireille Dardenne

Authors
  1. Françoise Homo-Delarche
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mireille Dardenne
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Homo-Delarche, F., Dardenne, M. The neuroendocrine-immune axis. Springer Semin Immunopathol 14, 221–238 (1993). https://doi.org/10.1007/BF00195975

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00195975

Keywords

Search

Navigation