INSULIN THERAPY OF PREDIABETES SUPPRESSES TH1 ASSOCIATED GENE-EXPRESSION IN BB RAT PANCREAS

Subcutaneous insulin treatment of young diabetes prone BB rats has bee n shown previously to suppress the development of autoimmune diabetes. In this study the hypothesis was tested that exogenous insulin may de viate the autoimmune process by acting on the Th1/Th2 cytokine balance in the pancreas. BB rats were implanted with pellets which continuous ly released insulin, at 50 d of age. Three weeks later cytokine mRNA e xpression in the pancreas and insulitis score were determined. While i n control BB rats high levels of IFN gamma mRNA were detectable by RT- PCR, insulin treatment almost completely suppressed IFN gamma mRNA lev els without concomitant upregulation of counterregulatory IL-10 and TG F beta gene expression. Insulin also suppressed gene expression of ind ucible nitric oxide synthase. Mean insulitis scores were decreased aft er insulin treatment. We conclude that the protective effects of insul in treatment may not be due to the induction of protective Th2 immune reactivity but to general downregulation of immune activation in the p ancreas, and hence also of Th1 autoimmunity.