Acromegaly and immune function

GH/IGF-I axes have long been supposed to play a major role in immunomodulation. They ensure ordered body growth and therefore are involved in complex interactions with most organ systems, tissues, and cell types. The homozygous Snell-Bagg dwarf mouse, GH-, PRL-, and thyroid hormones-deficient, has an associated poorly developed immune system including a marked spleen and thymus hypertrophy, a progressive loss of small lymphocytes in the thymic cortex, and a decreased number of peripheral blood lymphocytes. On the other hand, lymphoid cells themselves produce GH: 10% of unstimulated human peripheral blood mononuclear cells (PBMCs) were positive for GH, whereas after mitogen stimulation 20% were positive. A paracrine effect of thymocyte-secreted GH on human primary thymic epithelial cell (TEC) cultures has also been observed. Moreover, somatostatin and GH receptors are expressed in either human TEC or thymocytes. Both these types of receptor seem to be developmentally and differentially expressed on thymic cells, suggesting a crucial role of the local somatostatin-GH-IGF-I system in immune cell differentiation. Cytokines other than GH affect IGF-I synthesis in lymphoid tissues, e.g. in macrophages tumor necrosis factor-α (TNF-α) regulates IGF-I production, the colony-stimulating factors induce the expression of IGF-I mRNA, and the T cell-derived cytokine IFN-γ reduces IGF-I mRNA in a time- and dose-dependent manner. Therefore, the possibility that GH and IGF-I may have effects on immune responses in nonstressed, healthy animals that are compensated by the overlapping actions of other hormones or cytokines cannot be ruled out. Some changes in the lymphocyte subset pattern have been found in acromegaly, but whether these changes play a role in the increased prevalence of neo-plasms is still unknown.