Functional IL-18 Is produced by primary pancreatic mouse islets and NIT-1 beta cells and participates in the progression towards destructive insulitis.
Frigerio S., Holländer GA., Zumsteg U.
BACKGROUND: Preclinical stages of type 1 diabetes are characterized by infiltrating T cells and by the peri- and intra-islet accumulation of pro-inflammatory mediators, such as IFNgamma. METHODS/RESULTS: Using quantitative PCR we demonstrated that mRNA specific for the IFNgamma-inducing cytokine IL-18 is upregulated in NIT-1 beta cells and intact mouse islets upon exposure to IL-1beta, IFNgamma and TNFalpha. The biological activity of IL-18 was blocked using caspase inhibitors and anti-IL-18 antibodies. Increased IL-18 expression was also detected in islets during advanced stages of insulitis and correlated with elevated transcripts for IFNgamma and for the IL-18 receptor. CONCLUSION: Thus, beta cells produce bioactive IL-18 in the course of insulitis and actively contribute to the exacerbation of inflammation leading to their own demise.