T helper type 1 and 2 cytokines mediate the onset and progression of type I (insulin-dependent) diabetes

Type I (insulin-dependent) diabetes mellitus (IDDM) is an autoimmune diseas e that results from the destruction of insulin-secreting pancreatic islet b eta-cells by autoreactive cells and their mediators. Although its exact cau se is not completely understood, it is well established that IDDM is associ ated with dysregulated humoral and cellular immunity, exemplified by altere d production of and response to macrophage- and T cell-derived cytokines an d a shift in T helper (Th) cell differentiation in favor of a pathogenic Th 1 pathway. Th1 cytokines, including interleukin-a and interferon-gamma, ind uced islet beta-cell destruction directly by accelerating activation-induce d cell death (apoptosis) and by up-regulating the expression of select adhe sion molecules, Th1 cytokines facilitated the pancreatic homing of autoreac tive leukocytes, hence enhancing beta-cell destruction. More recently, a ro le for Th2 cytokines in IDDM pathogenesis was described. Accordingly, local production of Th2 cytokines, in particular interleukin-10, accelerated bet a-cell destruction by enhancing autoreactive cell infiltration of the pancr eas (insulitis) through modulation of the release of other cytokines and by modulating the microvasculature. Whereas both Th1 and Th2 cytokines are pr esent in peripheral T cells and in the pancreas in IDDM, the mechanism of a ction and the kinetics of a cell damage induced by Th1 and Th2 cytokines ap peared to be distinct. Collectively, this supports the idea that IDDM is no t an exclusive Th1-mediated disorder as was suggested, and that both Th1 an d Th2 cells and their respective mediators participate and cooperate in ind ucing and sustaining pancreatic islet beta-cell destruction in IDDM.