Function of rat pancreatic islets exposed to interleukin-18 in vitro

The recently cloned cytokine interleukin-18 (IL-18) has been shown to promo te a Th1-cell immune response, which may he a prerequisite for development of Type 1 diabetes. In this study we examined the effects of IL-18 on the f unction of isolated rat pancreatic islets. The islets were cultured in medi um RPMI 1640 + 10% fetal calf serum and exposed far 48 h to recombinant hum an IL-18 (0, 0.1, 1 and 10 nM). In some experiments IL-18 (10 nM) was combi ned with interleukin-12 (10 ng/ml), since these cytokines may act synergist ically. IL-18 alone, or in combination, with IL-12 did not affect the islet DNA content suggesting absence of cytotoxicity. However, both cytokines in duced an increased islet insulin content compared to non-cytokine exposed c ontrol islets. A slight increase in the medium insulin accumulation was obs erved when 1.0 nM IL-18 was added, but not in other experimental groups. Gl ucose-stimulated insulin release, glucose oxidation and (pro)insulin biosyn thesis rates were not affected by the cytokines after culture. In acute exp eriments IL-18 had a small stimulatory effect on glucose-stimulated insulin secretion. It was also tested if IL-18 (10 nM) could affect IL-1 beta (25 U/ml) induced suppression of the glucose oxidation rate, but this was not t he case. We conclude that IL-18 has minor stimulatory effects on beta-cell function, and no clear synergistic effect is observed when IL-12 is added t ogether with IL-18. If IL-18 is involved in beta-cell destruction in Type 1 diabetes, it is Likely that this effect is secondary to an influence on th e action of other cytokines.