Function of Rat Pancreatic Islets Exposed to Interleukin-18 In Vitro

Abstract

The recently cloned cytokine interleukin-18 (IL-18) has been shown to promote a Thl-cell immune response, which may be a prerequisite for development of Type I diabetes. In this study we examined the effects of IL-18 on the function of isolated rat pancreatic islets. The islets were cultured in medium RPMI 1640 f 10% fetal calf serum and exposed for 48h to recombinant human IL-18 (0, 0.1, 1 and IO nM). In some experiments IL-18 (10 nM) was combined with interleukin-12 (10ng/ml), since these cytokines may act synergistically. 1L-18 alone, or in combination, with IL-12 did not affect the islet DNA content suggesting absence of cytotoxicity. However, both cytokines induced an increased islet insulin content compared to non-cytokine exposed control islets. A slight increase in the medium insulin accumulation was observed when 1.0 nM IL-18 was added, but not in other experimental groups. Glucose-stimulated insulin release, glucose oxidation and (pro)insulin biosynthesis rates were not affected by the cytokines afterculture. In acute experiments IL-18 had a small stimulatory effect on glucose-stimulated insulin secretion. It was also tested if IL-18 (10 nM) could affect 1L-1β (25 U/ml) induced suppression of the glucose oxidation rate, but this was not the case. We conclude that IL-18 has minor stimulatory effects on β-cell function, and no clear synergistic effect is observed when IL-12 is added together with IL-18. If IL-18 is involved in β-cell destruction in Type I diabetes, it is likely that this effect is secondary to an influence on the action of other cytokines.

Key Words:

• Interleukin-18
• Interleukin-12
• Insulin secretion
• Pancreatic islets