Possible role of IL-1, TNF-alpha, and IL-6 in insulin-dependent diabetes mellitus and autoimmune thyroid disease. Thyroid Cell Group

Recent experiments indicate a central role of macrophages (M phi), and natural killer (NK) cells, and their products IL-1, IL-6 and TNF alpha in autoimmune endocrine diseases. Intermediate levels of IL-1 alpha/beta inhibit the function of pancreatic beta-cells and thyrocytes, an effect potentiated by TNF alpha. In contrast, low levels of IL-1 potentiate the secretion of insulin and thyroid hormones, and intermediate levels of IL-6 double glucose-induced insulin production by beta-cells. Intermediate and high levels of IL-1 and IL-6 are cytotoxic to normal beta-cells. IL-1 induces IL-6 in isolated islets and in thyrocytes. The cytokines may play a role in the physiological regulation of endocrine functions, for instance during conditions of stress. The genes for TNF alpha and -beta, both located in the MHC region, and IL-6 are polymorphic, and specific alleles may control the amount of cytokine produced. Specific TNF alpha/beta alleles may be in linkage disequilibrium with HLA alleles known to be positively or negatively associated with endocrine and other autoimmune diseases.