Sex hormones and the immune system--Part 2. Animal data.

Sex hormones have physiological and pathological (autoimmune conditions) effects on the immune system. Studies in experimental animal models of human autoimmune diseases have clearly shown that sex hormones regulate the expression, severity and course of autoimmune diseases. Sex hormones affect the function of T, B and NK cells, and macrophages. Precisely how sex hormones affect lymphocytes is a highly complex question. Sex hormones can modulate the immune system, perhaps directly (e.g. thymic reticular tissue), or indirectly via host and many oestrogen target tissues, including the central nervous system hypothalamic-pituitary axis (the neuroendocrine tissues). The effects of sex hormones on the immune system (immunosuppression or immunopotentiation) may vary, even with the same hormone. For example, oestrogen can increase IgA levels in the uterus, but decrease IgA levels in the vagina or have no effect in lacrimal tissues (Sullivan, 1989). Therefore the effects of sex hormones on the immune system cannot be generalized but must be evaluated independently. Some of the reasons for variability in results have been reviewed in detail elsewhere (Steinberg et al, 1979; Ansar Ahmed et al, 1985b). These include, dose of hormones, age and sex-hormonal status of animals, route and time of administration, the immunocompetence of the host, stress, the metabolism of hormones (e.g. metabolism of testosterone to oestrogen) resulting in alteration of biological activity, and differential response to various antigens. The initial encounter of sex hormones with the type of target cells, the variability of secondary messengers and gene activation events are other important considerations. The effects of sex hormones on the immune system to modulate immune responses are unequivocal. The burgeoning advances in cellular immunology, endocrinology and molecular biology, should provide a better understanding of: (1) the interactions of hormones with the immune system; (2) how hormones activate specific genes; and (3) how hormones influence intracellular communication. In a clinical situation, it is hoped that androgenic compounds which lack virilizing effects, but possessing the desired immunomodulatory effects, will eventually be synthesized. These hormone analogues, in combination with specific (non-toxic) oestrogen antagonists, may offer new therapeutic avenues.