doiSerbia

Interaction involving the thymus and the hypothalamus-pituitary axis, immunomodulation by hormones

Marković Ljiljana (Institut za patološku fiziologiju, Medicinski fakultet, Beograd)

Perfectly projected and impeccably created, the endocrine system precisely regulates the most delicate immune processes. The immune and neuroendocrine systems are two essential physiological components of mammalian organisms important for protection from the infection and disease on one hand, and on the other, for regulation of metabolism and other physiological activities; namely, the evidence has been found indicating that there is active and dynamic collaboration of these systems in the execution of their designated functions [1, 2,4]. These interactions occur at many stages of embryonic and neonatal development, and they are a continual part of normal homeostatic balance necessary to preserve health. There is communication between neuroendocrine and immune system via cytokines, neurotransmitters and peptide hormones which act, in both systems, through the same receptor molecules (Scheme 1). Many investigators have reported the increased thymic weight in experimental animals due to both castration and adrenalectomy [4]. The discovery from 1898 revealing that thymus was enlarged in castrated rabbits has been considered the embryo of hybrid medical discipline, i.e. the immunoendocrinology [1]. In the actual literature, at least in that available to us, it has not been noted that the appearance of the eunuchs, i.e. the castrates, stimulated the analytical approach to this phenomenon. Endocrine influences appear to be a part of bidirectional circuitry, namely, thymic hormones also regulate the release of hormones from the pituitary gland. Physiologically, thymus is under neuroendocrine control. It is apparent that the circulating levels of distinct peptide hormones are necessary to maintain a series of biological functions related both to micro environmental and lymphoid cells of the organ. The neuroendocrine control of the thymus appears to be extremely complex, with apparent presence of complete intrathymic biological circuitry involving the production of pituitary hormones, as well as the expression of their respective receptors by thymic cell [7-9]. The influence of gonadectomy on the humoral immunity has been controversial. All investigations agree that women have higher titres of all classes of circulating antibodies than men [1, 3]. The application of estrogens stimulated the formation of antibodies in the circulation [17]. Then, if there were no sex glands, the immune response of the individual would be enhanced. Both the cellular and the humoral immune response is more powerful in the adult normal women than in men of the same age. The immune response is different in different sexes meaning that there is a sexual dimorphism. This difference has not been noted before the puberty [4]. It has been noticed that the substitution therapy has alleviated the late skin hypersensitivity [9], The estrogens have also curtailed the rejection time of the transplant and all reactions in which T-effector lymphocytes have been involved. NK-cells and T-lymphocytes activities have been decreased by the action of estrogens, as well as the release of thymus hormones [27]. Cortical RE cells express a surface antigen, gp200-MR6, which plays a significant role in thymocyte differentiation [7, 9]. irrespectively of which pathway may be triggered by neuroendocrine factors, the effects are pleiotropic and result in modulation of the expression of several genes in different cell types. Thymic neuroendocrine polypep-tides are the source of self-antigens presented by MHC molecules enabling the differentiation of haematopoietic stem cells [10]. Thymic nurse cells also produce thymosins beta 3 and beta 4 and display a neuroendocrine cell specific immunophenotype (IP): Thy-1+, A2B5+, TT+TE4+, UJ13/A+, UJ127.11+, UJ167.11+, Š181.4+ and presence of common leukocyte antigen (CLA+) [7,16]. GH enhances thymocyte release from TNCs, as well as the reconstitution of these lymphoepithelial complexes [11]. Similar to its role as a regulator of bone metabolism through regulating osteoprotegerin (OPG) production, the estrogen is involved in the processes of thymocyte development although aromatase mRNA has not been detectable in the thymus. While the increase of TNC number during lactation may be linked to the process of reconstruction of the thymic lymphoid population, the increased activity of lymphoepithelial interactions on GD14 may be associated with thymic engagement in pregnancy-induced immune processes [27,29] The major antigens in the experimental autoimmune hypophysitis in rats are growth hormone, thyrotropin, and luteinizing hormone [12]. The intrathymic T-lymphocyte selection is a complex, multistep process, influenced by several functionally specialised RE cells and under immuno-neuroendocrine regulation control reflecting the dynamic changes of the mammalian organism. In HIV-1-infected adults treated with growth hormone [25 ], thymic mass and circulating naive CD4 T cells are increased. The treatment would be easier for the diseased, as well as to us, the physicians, if we were aware of two millennia old wisdom - that the disease is a visit of God.

Keywords: hypothalamus, pituitary, thymus, hormones, immunomodulation