The paradoxical effects of interleukin 10 in the immunoregulation of autoimmune diabetes.

Insulin-dependent diabetes mellitus (IDDM) is a chronic autoimmune disease and spontaneously develops in NOD mice and humans. The role of T helper 1 (Th1) and T helper 2 (Th2) cytokines in the immunopathogenesis of disease is not understood. IL-10 has presented a particularly paradoxical role. Transgenic (Tg) BALB/c mice expressing IL-10 in the pancreas exhibited periinsulitis but not insulitis and diabetes. However, backcrossing of these Tg mice with NOD mice accelerated the onset of diabetes, indicating a pathogenic role for IL-10 in the pathogenesis of autoimmune diabetes since it is able to replace the genetic susceptibility information on the NOD genome. Conversely, administration of IL-10 to adult NOD delayed the onset of and decreased the incidence of diabetes suggesting a potential therapeutic role for IL-10 in autoimmune diabetes. Overall, the findings indicated a paradoxical role for IL-10 in the immunoregulation of autoimmune diabetes.