THE EXPRESSION AND FUNCTION OF GH/IGF-I RECEPTORS IN THE IMMUNESYSTEM

In the last 70 years, an extensive body of literature has been published concerning the existence of a tight communicating network linking the neuroendocrine and immune systems through the presence of shared ligands and receptors. Much experimental evidence indicates that a similar communication link exists in the endocrine system between the GH/GH receptor/GH binding protein/IGF-I axis and the immune system, although the regulatory mechanisms differ some-what. Through endocrine, autocrine and paracrine mechanisms, GH and IGF-I contribute to regulate, in concert with cytokines, the development and function of the immune system. The agerelated modifications occurring within the primary lymphoid tissues is likely to be influenced by the effect of GH and IGF-I on immune cells. Virtually all of the cells of the immune system are targets of GH and IGF-I actions, as has been demonstrated both by the expression of their specific receptors by radioligand assays and, more recently, by flow cytometry. GH and IGF-I have stimulatory effects on the proliferation of immunocompetent cells and regulate several cellular and humoral functions. These growth factors have also been shown to have both thymopoietic and myelopoietic effects in immuno-deficient animals. Moreover, in vitro experiments indicate that these hormones are able to increase immunoglobulin secretion by normal and transformed B lymphocytes, to enhance the cytotoxic activity of natural killer cells, and to activate contact sensitivity reactions, graft rejections and graft versus host reactions. Despite the pleiotropic effects of GH and IGF-I on the immune system, only minor alterations have been described in GH deficient subjects, probably due to a more pronounced redundancy in the hormonal control of the human immune system with respect to that in experimental animals. Although much has been learned, many critical questions remain unanswered on the clinical importance of the interaction between GH, IGF-I and the immune system such as the potential role of these hormones as: (1) immunotherapeutic agents in clinical states of immunodeficiency, (2) immunomodulants in critically ill patients, and (3) enhancers of malignant hematopoiesis