Journal of Adolescent Health
Volume 30, Issue 4, Supplement 1 , Pages 59-70 , April 2002

Gender differences in the development and function of the immune system

  • Richard S Shames, M.D.

      Affiliations

    • Corresponding Author InformationAddress correspondence to: Richard S. Shames, M.D., Assistant Clinical Professor of Pediatrics, Division of Allergy and Clinical Immunology, Room G309, Stanford University Medical Center, Stanford, CA 94305-5208 USA
    • Division of Allergy and Clinical Immunology, Stanford University Medical Center, Stanford, California, USA

,Accepted 14 September 2001.

References 

  1. Lahita RG. Sex hormones and the immune system—part I. Human data. Bailliere’s Clin Rheumatol. 1990;4:1–12
  2. Ahmed SA, Talal N. Sex hormones and the immune system—part 2. Animal data. Bailliere’s Clin Rheumatol. 1990;4:13–31
  3. Arythrea BH. Hypophseal-Pituitary-Adrenal axis in autoimmune and rheumatic diseases. Immunol Res. 1998;18:93–102
  4. Task Force on Gender MSaA Whitacre CC, Reingold SC, O’Looney PA. A gender gap in autoimmunity. Science. 1999;283:1277–1278
  5. The Task Force on Gender MSaA . Sex Differences in Autoimmune Disease (Focus on Multiple Sclerosis). New York: National Multiple Sclerosis Society; 1999;
  6. Jacobson DL, Gange SJ, Rose NR, Graham NMH. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol. 1997;84:223–243
  7. Beeson PB. Age and sex associations of 40 autoimmune diseases. Am J Med. 1994;96:457–462
  8. Hochberg MC, Spector TD. Epidemiology of rheumatoid arthritis (Update). Epidemiol Rev. 1990;12:247–252
  9. Rosciszewska D. Analysis of seizure dispersion during menstrual cycle in women with epilepsy. Monogr Neural Sciences. 1980;5:280–284
  10. Zorgdrager A, De Keyser J. Menstrually related worsening of symptoms in multiple sclerosis. J Neurol Sci. 1997;149:95–97
  11. Ostersen M, Aune B, Husby G. Effects of pregnancy and hormonal changes on the activity of rheumatoid arthritis. Scand J Rheumatol. 1983;12:69–72
  12. Petri M. Pregnancy in SLE. Bailliere’s Clin Rheumatol. 1998;12:449–476
  13. Arnason BG, Richman DP. Effect of oral contraceptives on experimental demyelinating disease. Arch Neurol. 1969;21:103–108
  14. Liang MH, Karlson EW. Female hormone therapy and the risk of developing or exacerbating systemic lupus erythematosus or rheumatoid arthritis. Proceedings of the Association of American Physicians. 1996;108:25–28
  15. Lahita RG. Sex steroids and rheumatic diseases. Arthritis Rheum. 1985;28:121–126
  16. Weinshenker BG, Rice GP, Noseworthy JH, et al.  The natural history of multiple sclerosis (A geographically based study. 3. Multivariate analysis of predictive factors and models of outcome). Brain. 1991;114:1045–1056
  17. Molina JF, Drenkard C, Molina J, et al.  Systemic lupus erythematosus in males. A study of 107 Latin American patients. Medicine. 1996;75:124–130
  18. Venn A, Lewis S, Cooper M, et al.  Questionnaire study of effect of sex and age on the prevalence of wheeze and asthma in adolescence. Br Med J. 1998;316:1945–1946
  19. Aberg N, Engstrom I. Natural history of allergic diseases in children. Acta Paediatr Scand. 1990;79:206–211
  20. Jenkins MA, Hopper JL, Bowes G, et al.  Factors in childhood as predictors of asthma in adult life. Brit Med J. 1994;309:90–93
  21. Skobeloff EM, Spivey WH, St. Clair SS, Schoffstall J. The influence of age and sex on asthma admissions. JAMA. 1992;268:3437–3440
  22. Settipane RA, Simon RA. Menstrual cycle and asthma. Ann Allergy Asthma Immunol. 1989;63:373–378
  23. Shames RS, Heilbron DC, Janson SL, et al.  Clinical differences among women with and without self-reported perimenstrual asthma. Ann Allergy Asthma Immunol. 1998;81:65–72
  24. Eliasson O, Scherzer HH, DeGraff AC. Morbidity in asthma in relation to the menstrual cycle. J Allergy Clin Immunol. 1986;77:87–94
  25. Troisi RJ, Speizer FE, Willett WC, et al.  Menopause, postmenopausal estrogen preparations, and the risk of adult-onset asthma. A prospective cohort study. Am J Respir Crit Care Med. 1995;152:1183–1188
  26. Brick JC, Wilson DA, Walker SA. Hormonal modulation of responses to thymus-independent and thymus-dependent antigens in autoimmune NZB/NZW mice. J Immunol. 1985;134:3603–3608
  27. Roubinian J, Talal N, Siiteri PK, Sadakian JA. Sex hormone modulation of autoimmunity in NZB/NZW mice. Arthritis Rheum. 1979;22:1162–1169
  28. Roubinian J, Talal N, Greenspan JS, et al.  Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice. J Exp Med. 1978;147:1568–1583
  29. Roubinian JR, Papoian R, Talal N. Androgenic hormones modulate autoantibody responses and improve survival in murine lupus. J Clin Invest. 1977;59:1066–1070
  30. Chrousos GP. The hypothalamic-pituitary adrenal axis and immune-mediated inflammation. N Engl J Med. 1995;332:1351–1362
  31. Sternberg EM, Scott-Young W, Bernadini R, et al.  A central nervous system defect in the biosynthesis of corticotropin-releasing hormone is associated with susceptibility to streptococcal cell wall induced arthritis in Lewis rats. Proceedings of the National Academy of Science. 1989;86:4771–4775
  32. Chikanza I, Petrou P, Kingsley G, et al.  Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis. Arthritis Rheum. 1992;35:1281–1288
  33. Neeck G, Federlin K, Graef V, et al.  Adrenal secretion of cortisol in patients with rheumatoid arthritis. J Rheumatol. 1990;17:24–29
  34. Berczi I. The role of the growth and lactogenic hormone family in immune function. Neuroimmunomodulation. 1994;1:201–216
  35. Waldstreicher J, Duffy JF, Brown EN, et al.  Gender differences in the temporal organization of prolactin (PRL) secretion (Evidence for a sleep-independent circadian rhythm of circulating PRL levels—a clinical research center study). J Clin Endocrinol Metab. 1996;81:1483–1487
  36. Yao DL, Liu X, Hudson LD, Webster HD. Insulin-like growth factor I treatment reduces demyelination and up-regulates gene expression of myelin-related proteins in experimental autoimmune encephalomyelitis. Proceedings of the National Academy of Sciences of the United States of America. 1995;92:6190–6194
  37. Ho KK, O’Sullivan AJ, Weissberger AJ, Kelly JJ. Sex steroid regulation of growth hormone secretion and action. Horm Res. 1996;45:67–73
  38. Fink G. Oestrogen and progesterone interactions in the control of gonadotrophin and prolactin secretion. J Steroid Biochem. 1988;30:169–178
  39. Sthoegher ZM, Chirozi M, Lahita RG. Regulation of the immune response by sex hormones I. Effects of estradiol and testosterone on pokeweed mitogen induced human B cell differentiation. J Immunol. 1988;141:91–98
  40. Lichtman MA, Vaughan JH, Hames CG. The distribution of serum immunoglobulins, anti-gamma-G globulins (“rheumatoid factors”) and antinuclear antibodies in White and Negro subjects in Evans County, Georgia. Arthritis Rheum. 1967;10:204–215
  41. Sullivan DA. Hormonal influence on the secretory immune system of the eye. In:  Frier S editors. The Neuroendocrine-Immune Network. Boca Raton, FL: CRC Press; 1989;
  42. Gusdon JP. Fetal and maternal immunoglobulin levels during pregnancy. Am J Obstet Gynecol. 1969;103:895–900
  43. Farnam J, Lavastida MT, Grant JA, et al.  Antinuclear antibodies in the serum of normal pregnant women. J Allergy Clin Immunol. 1984;73:596–599
  44. Graff RJ, Lappe MA, Snell GD. The influence of the gonads and the adrenal glands on the immune response to skin grafts. Transplantation. 1969;7:105–111
  45. Dresser DW. Specific inhibition of antibody production I. Protein over-loading paralysis. Immunology. 1962;5:161–168
  46. Gross L. Influence of sex on the evolution of a transplant mouse sarcoma. Proceedings for the Society for Experimental Biology and Medicine. 1941;47:273–276
  47. Weinstein Y, Ran S, Segal S. Sex-associated differences in the regulation of immune responses controlled by the MHC of the mouse. J Immunol. 1984;132:656–661
  48. Amadori A, Zamarchi R, De Silvestro G, et al.  Genetic control of the CD4/CD8 T-cell ratio in humans. [see comments] Nat Med. 1995;1:1279–1283
  49. Weinstein Y, Berkovich Z. Testosterone effect on bone marrow, thymus and suppressor T cells in NZB x NZW F1 mice (Its relevance to autoimmunity). J Immunol. 1981;126:998–1002
  50. Cohen JH, Danel L, Cordier G, et al.  Sex steroid receptors in peripheral T cells (Absence of androgen receptors and restriction of estrogen receptors to OKT8-positive cells). J Immunol. 1983;131:2767–2771
  51. Carlsten H, Tarkowski A, Holmdahl R, Nilsson LA. Oestrogen is a potent disease accelerator in SLE-prone MRL lpr/lpr mice. Clin Exp Immunol. 1990;80:467–473
  52. Paavonen T, Anderson LC, Adlercreutz H. Sex hormone regulation of in vitro immune responses. J Exp Med. 1981;154:1935–1945
  53. Stimson WH. Oestrogen and human T lymphocytes (Presence of specific receptors in the T-suppressor/cytotoxic subset). Scand J Immunol. 1988;28:345–350
  54. Magalhaes MM, Magalhaes MC. Effects of ovariectomy and estradiol administration on the adrenal macrophage system of the rat. Cell Tissue Res. 1984;238:559–564
  55. Roberts BV. The effects of steroid hormones on macrophage activity. Int Rev Cytol. 1969;25:131–159
  56. Boorman GA, Luster MI, Dean JH, Wilson RE. The effect of adult exposure of diethylstilbesterol in the mouse on macrophage function and numbers. J Reticuloendothelial Soc. 1980;28:547–559
  57. Flynn A. Expression of Ia and the production of interleukin-1 by peritoneal exudate macrophages activated in vivo by steroids. Life Sciences. 1986;38:2455–2460
  58. George FW. Androgen metabolism in the prostate of the finasteride-treated, adult rat (A possible explanation for the differential action of testosterone and 5 alpha-dihydrotestosterone during development of the male urogenital tract). Endocrinology. 1997;138:871–877
  59. Danel L, Vincent C, Rousset F, et al.  Estrogen and progesterone receptors in some human myeloma cell lines and murine hybridomas. J Steroid Biochem. 1988;30:363–367
  60. Gilmore W, Weiner LP, Correale J. Effect of estradiol on cytokine secretion by proteolipid protein-specific T cell clones isolated from multiple sclerosis patients and normal control subjects. J Immunol. 1997;158:446–451
  61. Pettersson K, Grandien K, Kuiper GG, Gustafsson JA. Mouse estrogen receptor beta forms estrogen response element-binding heterodimers with estrogen receptor alpha. Mol Endocrinol. 1997;11:1486–1496
  62. Venkov CD, Rankin AB, Vaughan DE. Identification of authentic estrogen receptor in cultured endothelial cells. A potential mechanism for steroid hormone regulation of endothelial function. Circulation. 1996;94:727–733
  63. Weiss K, Wagener D. Changing patterns of asthma mortality. Identifying target populations at high risk. JAMA. 1990;264:1683–1687
  64. Sasson S, Mayer M. Effect of androgenic steroids on rat thymus and thymocytes in suspension. J Steroid Biochem. 1981;14:509–518
  65. Sobhon P, Jirasattham C. Effects of sex hormones on the thymus and lymphoid tissue of ovariectomized rats. Acta Anat. 1974;89:211–225
  66. Chiodi H. The relationship between the thymus and sex organs. Endocrinology. 1940;26:107–135
  67. Olsen NJ, Viselli SM, Shults K, et al.  Induction of immature thymocyte proliferation after castration of normal male mice. Endocrinology. 1994;134:107–113
  68. Grossman CJ. Regulation of the immune system by sex steroids. Endocr Rev. 1984;5:435–455
  69. Olsen NJ, Watson MB, Henderson GS, Kovacs WJ. Androgen deprivation induces phenotypic and functional changes in the thymus of adult male mice. Endocrinology. 1991;129:2471–2476
  70. Screpanti I, Morrone S, Meco D, et al.  Steroid sensitivity of thymocyte subpopulations during intrathymic differentiation. Effects of 17 beta-estradiol and dexamethasone on subsets expressing T cell antigen receptor or IL-2 receptor. J Immunol. 1989;142:3378–3383
  71. Okuyama R, Abo T, Seki S, et al.  Estrogen administration activates extrathymic T cell differentiation in the liver. J Exp Med. 1992;175:661–669
  72. Wilson CA, Mrose SA, Thomas DW. Enhanced production of B lymphocytes after castration. Blood. 1995;85:1535–1539
  73. Medina KL, Kincade PW. Pregnancy-related steroids are potential negative regulators of B lymphopoiesis. Proceedings of the National Academy of Science. 1994;91:5382–5386
  74. Masuzawa T, Miyaura C, Onoe Y, et al.  Estrogen deficiency stimulates B lymphopoiesis in mouse bone marrow. J Clin Invest. 1994;94:1090–1097
  75. McEwen BS, Alves SE, Bulloch K, Weiland NG. Ovarian steroids and the brain (Implications for cognition and aging). Neurology. 1997;48(5 Suppl 7):)S8–)S15
  76. Kuiper GG, Gustafsson JA. The novel estrogen receptor-beta subtype (Potential role in the cell- and promoter-specific actions of estrogens and anti-estrogens). FEBS Lett. 1997;410:87–90
  77. Prabhala RH, Wira CR. Sex hormone and IL-6 regulation of antigen presentation in the female reproductive tract mucosal tissues. J Immunol. 1995;155:5566–5573
  78. Allen JE, Maizels RM. Th1-Th2 (Reliable paradigm or dangerous dogma?). [see comments] Immunol Today. 1997;18:387–392
  79. Huygen K, Palfliet K. Strain variation in interferon gamma production of BCG-sensitized mice challenged with PPD II. Importance of one major autosomal locus and additional sexual influences. Cell Immunol. 1984;85:75–81
  80. Gallichan WS, Rosenthal KL. Effects of the estrous cycle on local humoral immune responses and protection of intranasally immunized female mice against herpes simplex virus type 2 infection in the genital tract. Virology. 1996;224:487–497
  81. Barna M, Komatsu T, Bi Z, Reiss CS. Sex differences in susceptibility to viral infection of the central nervous system. J Neuroimmunol. 1996;67:31–39
  82. Hildeman D, Yanez D, Pederson K, et al.  Vaccination against persistent viral infection exacerbates CD4+ T-cell-mediated immunopathological disease. J Virol. 1997;71:9672–9678
  83. Quinn DG, Zajac AJ, Frelinger JA, Muller D. Transfer of lymphocytic choriomeningitis disease in beta 2-microglobulin-deficient mice by CD4+ T cells. Int Immunol. 1993;5:1193–1198
  84. Padgett DA, Loria RM, Sheridan JF. Endocrine regulation of the immune response to influenza virus infection with a metabolite of DHEA-androstenediol. J Neuroimmunol. 1997;78:203–211
  85. Warner JA, Jones CA, Jones AC, et al.  Immune responses during pregnancy and the development of allergic disease. Pediatr Allergy Immunol. 1997;8:5–10
  86. Fox HS, Bond BL, Parslow TG. Estrogen regulates the IFN-gamma promoter. J Immunol. 1991;146:4362–4367
  87. Hu SK, Mitcho YL, Rath NC. Effect of estradiol on interleukin 1 synthesis by macrophages. Int J Immunopharmacol. 1988;10:247–252
  88. Stites DP, Siiteri PK. Steroids as immunosuppressants in pregnancy. Immunol Rev. 1983;75:117–138
  89. Piccinni MP, Giudizi MG, Biagiotti R, et al.  Progesterone favors the development of human T helper cells producing Th2-type cytokines and promotes both IL-4 production and membrane CD30 expression in established Th1 cell clones. J Immunol. 1995;155:128–133
  90. Correale J, Arias M, Gilmore W. Steroid hormone regulation of cytokine secretion by proteolipid protein-specific CD4+ T cell clones isolated from multiple sclerosis patients and normal control subjects. J Immunol. 1998;161:3365–3374

PII: S1054-139X(01)00382-2

Journal of Adolescent Health
Volume 30, Issue 4, Supplement 1 , Pages 59-70 , April 2002

Article Tools

* Image Usage & Resolution