THE PARADOXICAL EFFECTS OF INTERLEUKIN-10 IN THE IMMUNOREGULATION OF AUTOIMMUNE DIABETES

Insulin-dependent diabetes mellitus (IDDM) is a chronic autoimmune dis ease and spontaneously develops in NOD mice and humans. The role of T helper 1 (Th1) and T helper 2 (Th2) cytokines in the immunopathogenesi s of disease is not understood. IL-10 has presented a particularly par adoxical role. Transgenic (Tg) BALB/c mice expressing IL-10 in the pan creas 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-IO in the pathogenesis o f autoimmune diabetes since it is able to replace the genetic suscepti bility information on the NOD genome. Conversely, administration of IL -10 to adult NOD delayed the onset of and decreased the incidence of d iabetes suggesting a potential therapeutic role for IL-10 in autoimmun e diabetes. Overall, the findings indicated a paradoxical role for IL- 10 in the immunoregulation of autoimmune diabetes. (C) 1996 Academic P ress Limited