A growing amount of evidences suggest that the immune system interacts with both the nervous and endocrine systems. In this review we shall focus on the experimental evidence concerning the mutual influences of the gonads and the immune system cells and products. Clinical and experimental evidence have shown that infection produced by some virus, bacteria as well as parasites, modify the serum concentrations of sex steroid hormones. Gonad steroid hormones are now recognized to be intimately involved in the development and function of the thymus and the bursa of Fabricius. On the other hand thymic hormones have been shown to influence pituitary and gonad function. Evenmore, the potential role of white cells and their products in paracrine communication in the ovary and the testis has been receiving particular attention. Interleukins, which are locally produced in the gonads, influence steroidogenesis, ovulation and atresia. And, therefore, may be relevant for the physiology and pathology of the gonads. Understanding the crosstalk influence of the gonads with the immune system will nevertheless contribute to clarify many obscure facts in the physiology and pathology of immunity and reproduction.

Interactions between the immune, endocrine and nervous system constitute a hot field of research in today’s laboratories. Many scientists are now focusing on attempts to understand the molecular basis of interaction between these systems as well as their functional links. This understanding attempts to provide answers to questions concerning the physiology of regulatory mechanisms that control the immune response, as well as to understand the pathology deriving from the incorrect function of this system.

The influence of the immune system on reproduction is being intensively studied in order to know the origin of disturbances producing infertility in women and men. This article will focus on the functional interactions between immune system and the gonads, as well as their relevance to the physiology and pathology of the ovarian and testis cells. Perhaps the first bit of knowledge on immune and gonad interactions was obtained by the observations of Calzolari, who, at the end of the XIX century, demonstrated that the thymus of a castrated rabbit does not translate into the involution process that occurs at puberty. Years later Chioddi, showed that sex-hormone replacement in castrated rats reduced the volume of the thymus, resembling the pubertal involution of this organ, (1). After these significant findings, Greenstein et al (2), observed that the thymus, which had grossly atrophied in 12 to 15 month-old male rats, was markedly restored 30 days after orchidectomy. It is now a well known fact that the effects of gonadal steroids in the thymus are mediated by receptors. Cytosolic receptors for androgens, estrogens, and progesterone have been identified in the thymus (3-6). Furthermore, androgens accelerate thymocyte apoptosis in mice (7). Olsen et al (8), continues by stating that proliferation of these cells contribute to thymus enlargements after castration. Androgen receptor protein expression in the neonatal thymus does not reach significant levels until the animal is at least four weeks of age (9), a fact which may explain why neonatal thymus seems not to be greatly affected by the high physiological testosterone levels characteristic of the neonatal period. It must be stated that estrogens also induce thymic involution (5). It is also a well recognized fact, that the thymus is an endocrine gland, whose hormones are mediators in several steps of T cell differentiation. Some of these hormones have been chemically characterized and their amino acid sequences are now known as Thymosin alfa 1 (10), Thymopoietin (11), Thymulin (12), and Thymic Humoral Factor (13). Sex steroids can modulate in vitro Thymulin and Thymosin α 1 and β 4 production (14- 17). The production of some neuroendocrine hormones and neuropeptides by lymphocytes of both primary and secondary lymphoid organs have been also shown (18). In the last few years a considerable bulk of work has been undertaken to understand the influence of cytokines in the immune response system. Cytokines are proteins produced by immune cells as well as many other tissues. Their role in the secretion of steroid hormones is now intensively studied (19). Interleukin 6 (IL-6) has emerged as being a potent regulator of intracrine estrogen synthesis in breast tissues (20), thus promoting an estrogenic environment favoring tumor growth.

The development and function of another immune organ, the bursa of Fabricius, is also under the influence of androgens. The administration of testosterone in the first days of the development of the chick embryo markedly affects the size of the bursa (21), leaving the birds with an impaired B immune function. Receptors for androgens and estrogens have also been found in the bursal reticuloepitelial cells and lymphocytes. Early surgical removal of the bursa of Fabricius modified the development of the chick embryo testis and ovary while bursal grafts were able to restore the testis weight and function (22, 23). The addition of a bursal extract  inhibited human Chorionic Gonadotropin  (hCG)- dependent testosterone production by testis tissue in vitro (24). A partial characterization of an anti-steroidogenic peptide from the Bursa of Fabricius has been reported (25).