Klinische Wochenschrift

, Volume 64, Issue 1, pp 1–7 | Cite as

Endocrine regulation of the immune system

  • W. Kiess
  • B. H. Belohradsky


Immunoregulation, the major process of self-defence, appears to be more complex than has been previously thought, involving the central nervous and endocrine systems. This review demonstrates growing evidence for the hypothesis that endocrine factors from the pituitary and hypothalamus directly influence the development and function of the immune system. Both pituitary and hypothalamic hormones interfere with lymphocyte proliferation and function. Proliferation of T-lymphocytes as well as production of immunoglobulins by plasma cells seem to be hormone dependent. Clinical observations suggest that hematological, oncological, and immunological disorders known for their immune pathogenesis are associated with alterations of the endocrine homeostasis. Recently, human peripheral mononuclear cells have been shown to possess specific receptors for pituitary hormones. It is hypothesized that proteohormones act directly on lymphocytes via specific membrane receptors. Thus, the endocrine system, closely related to cortical and subcortical centers in the central nervous system, is one of the body's instruments to regulate and modulate its immune response. This hypothesized immunoregulatory pathway via the central nervous system and endocrine glands may well be of importance for the body's defence against infectious and malignant diseases. In addition, a new picture of the complex immunoregulatory mechanisms emerges for a better understanding of the function of the immune system. However, there is no single hormone which has yet been identified as being crucial for development and/or function of the immune system. It appears from the literature that a number of various proteohormones rather than a single hormone acts on immunocompetent cells.

Key words

Immunoregulation Proteohormones Lymphocytes Receptors Pituitary Hypothalamus Lymphocyte function 



adrenocorticotropic hormone


central nervous system


human chorionic gonadotropin


human growth hormone


mixed lymphocyte culture


natural killer






thyroid stimulating hormone


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Amino N, Mori H, Iwatani Y, Asari S, Izumiguchi Y, Miyai K (1982) Peripheral K lymphocytes in autoimmune thyroid disease: decrease in Graves' and increase in Hashimoto's disease. J Clin Endocrinol Metabol 54:587–591Google Scholar
  2. 2.
    Amman AJ, Duquesnoy RJ, Good RA (1970) Endocrinological studies in ataxia-teleangiectasia and other immunological deficiency diseases. Clin Exp Immunol 6:587–595Google Scholar
  3. 3.
    Astaldi A, Yalcin B, Meardi G, Burgio GR, Merolla R, Astaldi G (1973) Effect of HGH on lymphocyte transformation in cell culture. Blut 26:74–81Google Scholar
  4. 4.
    Atkinson S, Holcombe M, Kendall-Taylor P (1984) Ophthalmopathic immunoglobulin in patients with Graves' ophthalmopathy. Lancet II:374–376Google Scholar
  5. 5.
    Bach J-F (1983) (Ed) Thymic hormones Vol II, No 1 Clinics in Immunology and Allergy, W.B. Saunders Eastbourne, PhiladelphiaGoogle Scholar
  6. 6.
    Beck D, Ginsburg H, Naot Y (1977) The modulating effect of HCG on lymphocyte blastogenesis. Am J Obstet Gynecol 129:14–20Google Scholar
  7. 7.
    Berczi I, Nagy E (1981) Immunodeficiency in hypophysectomized rats: restoration by PRL. Fed Proc 40:1031Google Scholar
  8. 8.
    Buescher ES, Gallin JI (1984) Stature and weight in chronic granulomatous disease. J Pediatr 104:911–913Google Scholar
  9. 9.
    Burman KD, Baker JR Jr (1985) Immune mechanismus in Graves' disease. Endoc Rev 6:183–232Google Scholar
  10. 10.
    Van Buul-Offers S, van den Brande JL (1982) Cellular growth in organs of dwarf mice during treatment with GH, thyroxine, and plasma fractions containing somatomedin activity. Acta Endocrinol 99:150–160Google Scholar
  11. 11.
    Clarke WC, Weldon VV (1975) GH deficiency and Fanconi anemia. J Pediatr 86:814–815Google Scholar
  12. 12.
    Cross RJ, Markesbery WR, Brooks WH, Roszman TL (1984) Hypothalamic-immune interactions: neuromodulation of natural killer activity by lesioning of the anterior hypothalamus. Immunology 51:399–405Google Scholar
  13. 13.
    Desai LS, Lazarus H, Li CH, Foley GE (1973) Human leukemic cells. Effect of HGH. Exp Cell Res 81:330–332Google Scholar
  14. 14.
    Diaz-Espada F, Lopez-Alarcon L (1982) Mitogen-induced changes in glycolytic enzymes of mouse lymphocytes: influence of insulin on cell activation in vitro. Immunology 46:705–712Google Scholar
  15. 15.
    Dougherty TF (1952) Effect of hormones on lymphatic tissues. Physiol Rev 32:379Google Scholar
  16. 16.
    Dumont F, Robert F, Bischoff P (1979) T- and B-lymphocytes in pituitary dwarf Snell-Bagg mice. Immunology 38:23–31Google Scholar
  17. 17.
    Evered D, Whelan J (eds) (1982) Receptors, antibodies, and disease. Ciba Foundation, Pitman, LondonGoogle Scholar
  18. 18.
    Fabris N, Pierpaoli W, Sorkin E (1971) Hormones and the immunological capacity. III. The immunodeficiency disease of the hypopituitary Snell-Bagg dwarf mouse. Clin Exp Immunol 9:209–225Google Scholar
  19. 19.
    Fabris N, Pierpaoli W, Sorkin E (1971a) Hormones and the immunological capacity. IV. Restorative effects of developmental hormones or of lymphocytes on the immunodeficiency syndrome of the dwarf mouse. Clin Exp Immunol 9:227–240Google Scholar
  20. 20.
    Fawcett J, Hutton C, Mc Lachlan SM, Clark F, Rees-Smith B (1984) Defective regulation of the immune response to tetanus toxoid in Hashimoto's disease. Immunology 52:525–528Google Scholar
  21. 21.
    Ferguson FG, Cleland AW, Gambel PI, Confer FL (1982) Pregnancy and lactation induced suppression of cell mediated immunity. J Clin Lab Immunol 8:157–162Google Scholar
  22. 22.
    Fleischer TA, White RM, Broder S, Nissley SP, Blaese RM, Mulvihill JJ, Olive G, Waldmann TA (1980) X-linked hypogammaglobulinemia and isolated GH-deficiency. New Engl J Med 302:1429–1434Google Scholar
  23. 23.
    Forni G, Bindoni U, Santoni A, Bellnardo W, Marchese AE, Giovarelli M (1983) Radiofrequency destruction of the tuberoinfundibular region of hypothalamus permanently abrogates NK cells activity in mice. Nature 306:181–184Google Scholar
  24. 24.
    Friesen HG, Shiu RPC, Elsholtz H, Simpson S, Hughes J (1982) PRL and GH receptors. In: Receptors, antibodies, and disease, Evered D, J Whelan (eds) Pitman Ltd, London, pp 263–278Google Scholar
  25. 25.
    Fudenberg HH, Stites DP, Caldwell JL, Wells JV (1982) Basic and clinical immunology. Lange Med Publ, 3rd edition, Los AltosGoogle Scholar
  26. 26.
    Golde DW, Bersch N, Chopra JJ, Cline MJ (1977) Thyroid hormones stimulate erythropoisis in vitro. Br J Haematol 37:173–177Google Scholar
  27. 27.
    Golde DW, Bersch N, Li CH (1978) GH modulation of murine erythroleukemia cell growth in vitro. Proc Natl Acad Sci USA 75:3437–3439Google Scholar
  28. 28.
    Golde DW, Hersham HR, Lusis AJ, Groopman JE (1980) Growth factors. Ann Intern Med 92:650–662Google Scholar
  29. 29.
    Grinevich IA, El'chits TV (1981) Current concepts of the interaction between the body's endocrine and immune systems. Fiziol Zh 27:229–236Google Scholar
  30. 30.
    Hesketh PJ, Sullivan R, Valeri CR, McCaroll LA (1984) The production of granulocyte-monocyte colony stimulating activity by isolated human T-lymphocyte subpopulations. Blood 63:1141–1146Google Scholar
  31. 31.
    Iwatani Y, Amino N, Mori H, Asari S, Izumiguchi Y, Kumahara Y, Miyai K (1983) T-lymphocyte subsets in autoimmune thyroid disease and subacute thyroiditis detected with monoclonal antibodies. J Clin Endocrinol Metab 56:252Google Scholar
  32. 32.
    Jackson RA, Haynes BF, Burch WM, Shimizu K, Bowring MA, Eisenbarth GS (1984) Ia+ T cells in new onset Graves' disease. J Clin Endocrinol Metab 59:187–190Google Scholar
  33. 33.
    Johnsonbaugh RE, Ritzen EM, Hall K (1982) Hormonal influences on the growth of lectin-stimulated lymphocytes. European Society of Pediatric Endocrinology (ESPE) 21st Annual Meeting, HelsinkiGoogle Scholar
  34. 34.
    Katz DH (1977) Lymphocyte differentiation, recognition and regulation. Academic Press New YorkGoogle Scholar
  35. 35.
    Kiess W, Holtmann H, Butenandt O, Eife R (1983) Modulation of lymphoproliferation by HGH. Eur J Pediatr 140:47–50Google Scholar
  36. 36.
    Kiess W, Butenandt O (1985) Specific GH receptors on human peripheral mononuclear cells — re-expression, identification and characterization. J Clin Endocrinol Metab 60:740–746Google Scholar
  37. 37.
    Kiess W, Butenandt O (1985a) Effect of enzyme and enzyme inhibitors on specific binding of HGH to human peripheral lymphocytes. Acta Endocrinol 109:139–144Google Scholar
  38. 38.
    King M, Shaikh A, Bidwell D, Voller A, Banatvala JE (1983) Coxsackie-B-virus-specific IgM responses in children with insulin-dependent diabetes mellitus. Lancet I:1397–1399Google Scholar
  39. 39.
    Maddox J (1984) Psychoimmunology before its time. Nature 309:400Google Scholar
  40. 40.
    Martin-Du Pan RC, Dayer J-M (1982) Action des neurotransmitteurs et des médicaments psychotropes sur le système immunitaire. Schweiz Med Wochenschr 112:1910–1920Google Scholar
  41. 41.
    Melmed S, Braunstein GD (1983) HCG stimulates proliferation of Nb2 rat lymphoma cells. J Clin Endocrinol Metab 56:1068–1070Google Scholar
  42. 42.
    Mercola KE, Cline MJ, Golde DW (1981) GH stimulation of normal and leukemic human T-lymphocyte proliferation in vitro. Blood 58:337–340Google Scholar
  43. 43.
    Morse JH (1976) The effect of HCG and placental lactogen on lymphocyte transformation in vitro. Scand J Immunol 5:779–787Google Scholar
  44. 44.
    Nell LJ, Corbin JH, Wilson HK, Thomas JW (1982) The immune response to insulin: differential recognition of antigen by T and B cells. Clin Res 30:875AGoogle Scholar
  45. 45.
    Noble RL, Beer CT, Gout PW (1980) Evidence in vivo and in vitro of a role for the pituitary in the growth of malignant lymphomas in Nb rats. Cancer Res 40:2437–2440Google Scholar
  46. 46.
    Notario A, Paolini FA, Zocchi MT, Torriani A, Vitti MP (1983) Behavior of the principal protein hormones in normal and leukemic leucocytes. Arch Sci Med Torino 140:127–134Google Scholar
  47. 47.
    Ogawa K, Sueda K, Matsui N (1983) The effect of cortisol, progesterone and transcortin on PHA-stimulated human blood mononuclear cells and their interplay. J Clin Endocrinol Metab 56:121–126Google Scholar
  48. 48.
    Payan DG, Hess CA, Goetzl EJ (1984) Inhibition by somatostatin of the proliferation of T-lymphocytes and Molt-4 lymphoblasts. Cell Immunol 84:433–438Google Scholar
  49. 49.
    Pierpaoli W, Sorkin E (1968) Hormones and immunologic capacity. Effect of heterologous antigrowth hormone antiserum on thymus and peripheral lymphatic tissue in mice. Induction of a wasting syndrome. J Immunol 101:1036–1041Google Scholar
  50. 50.
    Pierpaoli W, Sorkin E (1969a) Effect of GH and anti-GH serum on the lymphatic tissue and the immune response. In: Sorkin E (ed) The immunresponse and its suppression. Karger, BaselGoogle Scholar
  51. 51.
    Pierpaoli W, Baroni C, Fabris N, Sorkin E (1969) Hormones and immunological capacity. II. Reconstitution of antibody production in hormonally deficient mice by somatotropic hormone, thyrotropic hormone and thyroxine. Immunology 16:217–230Google Scholar
  52. 52.
    Pierpaoli W, Fabris N, Sorkin E (1970) The effects of hormones on the development of the immune capacity. In: Cellular interaction in the immune response. 2nd Int Convoc Immunol, NY, Karger, Basel, p 25Google Scholar
  53. 53.
    Pirkle JC jr, Gann DS, Allen-Rowlands CF (1982) Role of the pituitary in restitution of blood volume after hemorrhage. Endocrinol 110:7–13Google Scholar
  54. 54.
    Renoux G, Biziere K, Renoux M, Guillaumin JM (1983) The production of T-cell-inducing factors in mice is controlled by the brain neocortex. Scand J Immunol 17:45–50Google Scholar
  55. 55.
    Rogers PC, Komp D, Rogol A, Sabio H (1977) Possible effects of GH on development of acute lymphoblastic leukemia. Lancet II:434Google Scholar
  56. 56.
    Roth JA, Lomax LG, Altszuler N, Hampshire J, Kaeberle J, Shelton ML, Draper DD, Ledet AE (1980) Thymic abnormalities and growth deficiency in dogs. Am J Vet Res 41:1256–1262Google Scholar
  57. 57.
    Rovensky J, Vigas M, Lokaj J, Cuncik P, Lukac P, Takac A (1982) Effect of growth hormone on the metabolic activity of phagocytes of peripheral blood in pituitary dwarfism and acromegaly. Endocrinol Exp (Bratislava) 16:129–134Google Scholar
  58. 58.
    Saxena QB, Saxena RK, Adler WH (1982) Regulation of natural killer activity in vivo. III. Effect of hypophysectomy and GH treatment on the natural killer activity of the mouse spleen cell population. Int Arch Allergy Appl Immunol 67:169–174Google Scholar
  59. 59.
    Shah SV, Wallis JD, Eilen SD (1983) Chemiluminescence and superoxide anion production by leukocytes from diabetic patients. J Clin Endocrinol Metab 57:402–409Google Scholar
  60. 60.
    Shambaugh GE, Beisel WR (1967) Early alterations in thyroid hormone physiology during acute infection in man. J Clin Endocrinol 27:1667–1673Google Scholar
  61. 61.
    Shavit Y, Lewis JW, Terman GW (1984) Opioid peptides mediate the suppressive effect of stress on natural killer cell cytotoxicity. Science 223:188–190Google Scholar
  62. 62.
    Snow EC, Feldbush TL, Oaks JA (1981) The effect of GH and insulin upon MLC response and the generation of cytotoxic lymphocytes. J Immunol 126:161–164Google Scholar
  63. 63.
    Sridana V, Pacini F, Degroot LJ (1982) Decreased suppressor T-lymphocytes in autoimmune thyroid diseases detected by monoclonal antibodies. J Clin Endocrinol Metab 54:316–319Google Scholar
  64. 64.
    Stiehm ER, Fulginiti VA (Eds) (1980) Immunologic disorders in infants and children. W.B. Saunders, PhiladelphiaGoogle Scholar
  65. 65.
    Theiss WC, Rupp GM, Varandani PT (1984) Insulin degrading activity in mononuclear and polymorphonuclear circulating leukocytes of non-diabetic subjects. J Clin Endocrinol Metab 59:344–349Google Scholar
  66. 66.
    Theofilopoulos AN, Dixon FJ (1982) Autoimmune disease: Immunopathology and etiopathogenesis. Am J Pathol 108:319–365Google Scholar
  67. 67.
    Thomas DW, Hoffmann MD (1984) Identification of macrophage receptors for angiotensin: a potential role in antigen uptake for T-lymphocyte responses. J Immunol 132:2807–2812Google Scholar
  68. 68.
    Weisz-Carrington P, Roux ME, McWilliams M, Phillips-Quagliata JM, Lamm ME (1978) Hormone induction of the secretory immune system in the mammary gland. Proc Natl Acad Sci USA 75:2928–2932Google Scholar
  69. 69.
    Wenzel B, Wenzel KW, Kotulla P, Schleusener H (1980) Suppressive effects of TSH n the antigen induced mitogenic response of human peripheral blood lymphocytes (PBL) Proc. 8th Int Thyroid Congress, SydneyGoogle Scholar
  70. 70.
    Whitfield JF, Macmanus JP, Rixon RH (1971) Stimulation by GH of deoxyribunucleic acid synthesis of rat thymic lymphocytes. Horm Metab Res 3:28–33Google Scholar
  71. 71.
    Wolstenholme GEW, Knight J (1970) Hormones and the immune response. CIBA Foundation, Study group no 36. Churchill, LondonGoogle Scholar
  72. 72.
    Yalcin B, Astaldi A (1973) With references to the effect of pituitary hormones on lymphocyte blastogenesis in cell culture. New Istanbul Contrib Clin Sci 10:188Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • W. Kiess
    • 1
    • 2
  • B. H. Belohradsky
    • 2
  1. 1.National Cancer Institute, Metabolism Branch National Institutes of HealthBethesdaUSA
  2. 2.Abteilung für Antimikrobielle Therapie und InfektionsimmunologieKinderklinik der Universität MünchenGermany

Personalised recommendations