IL-1 receptor deficiency slows progression to diabetes in the NOD mouse.

Proinflammatory cytokines are believed to be important in pancreatic beta-cell destruction in the development of type 1 diabetes. They act by upregulation of genes including Fas and inducible nitric oxide synthase (iNOS), which have both been shown to lead to beta-cell death in vitro. We used mice deficient in the interleukin (IL)-1 receptor (IL-1R) to assess the contribution of IL-1 to different models of diabetes. IL-1R-deficient islets were protected from the damaging effects of tumor necrosis factor (TNF) and interferon (IFN)-gamma in vitro, and beta-cell expression of iNOS was reduced, suggesting that IL-1 mediates the induction of iNOS by TNF and IFN-gamma. IL-1 action was not required for induction of class I major histocompatibility complex or Fas by TNF and IFN-gamma. IL-1R-deficient nonobese diabetic (NOD) mice developed diabetes significantly slower than wild-type mice. IL-1R deficiency did not affect diabetes in 8.3 TCR transgenic NOD mice but prolonged the time to diabetes in BDC2.5 TCR transgenic NOD mice. We conclude that IL-1R deficiency slows progression to diabetes in NOD mice but on its own does not prevent diabetes.