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.
Thomas
Helen E
HE
St. Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
Irawaty
Windy
W
Darwiche
Rima
R
Brodnicki
Thomas C
TC
Santamaria
Pere
P
Allison
Janette
J
Kay
Thomas W H
TW
D000818:Animals; D016923:Cell Death; D003433:Crosses, Genetic; D016207:Cytokines / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000276:immunology; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D007375:Interleukin-1 / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D007375:Interleukin-1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017472:Receptors, Interleukin-1