AN INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN PROTECTS INSULIN-PRODUCING BETA-CELLS AGAINST SUPPRESSIVE EFFECTS OF INTERLEUKIN-1-BETA

The cytokine interleukin-1-beta may have an important role in the autoimmune mediated damage of pancreatic Beta cells in insulin-dependent diabetes mellitus. In the present study we have investigated the effects of an interleukin-1 receptor antagonist protein. a blocker of the type I interleukin-1 receptor, on the suppressive actions of recombinant interleukin-1-beta on insulin-producing cells. Brief exposure (1-2 h) of rat and mouse pancreatic islets to 10 ng/ml recombinant interleukin-1-beta induced an 70-80% inhibition of insulin response to glucose after 12 h. These effects were completely counteracted by co-incubation with 100 ng/ml interleukin-1 receptor antagonist protein. When rat islets were cultured for 48 h in the presence of recombinant interleukin-l-beta (5 ng/ml) higher concentrations of interleukin-1 receptor antagonist protein (5000 ng/ml) were required to protect Beta-cell function. Interleukin-1 receptor antagonist protein also counteracted the inhibitory effects of recombinant interleukin-1-beta on the growth of the rat insulinoma cell line RINm5F. These data suggest that interleukin-I receptor antagonist protein can protect insulin-producing cells from the deleterious effects of recombinant interleukin-l-beta, and that these cells possess type I interleukin-I receptors.