Function of rat pancreatic islets exposed to interleukin-18 in vitro.
The recently cloned cytokine interleukin-18 (IL-18) has been shown to promote a Th1-cell immune response, which may be a prerequisite for development of Type 1 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 + 10% fetal calf serum and exposed for 48 h to recombinant human IL-18 (0, 0.1, 1 and 10 nM). In some experiments IL-18 (l0 nM) was combined with interleukin-12 (10 ng/ml), since these cytokines may act synergistically. IL-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 after culture. 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 IL-1beta (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 beta-cell function, and no clear synergistic effect is observed when IL-12 is added together 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 the action of other cytokines.
Krook
H
H
Department of Medical Cell Biology, Uppsala University, Sweden.
Wallström
J
J
Sandler
S
S
D000818:Animals; D046508:Culture Techniques; D003602:Cytotoxicity, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology; D020382:Interleukin-18 / Q000276:immunology* / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018417:Th1 Cells / Q000276:immunology
D020382:Interleukin-18; D018664:Interleukin-12