The effect of local production of cytokines in the pathogenesis of insulin-dependent diabetes mellitus

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease mediated by self-reactive T cells that induce inflammation and destruction of pancreatic islet β cells. A widely held belief is that T helper lymphocytes carrying a type 1 inflammatory phenotype are the major players in generating IDDM. However, recent evidence shows that cytokines belonging to the Th2 pathway can also induce autoimmune diabetes. The expression of cytokines directly within the pancreatic islets of transgenic mice helped to characterize the modulatory effects that Th1 or Th2 cytokines play on T cell- mediated autoimmune responses and diabetogenesis. This review describes the new information that these transgenic models have provided in understanding the exceedingly complex cytokine network and its role in the pathogenesis of IDDM.