Effects of interleukin-15 on suppression of rat pancreatic islets in vitro induced by proinflammatory cytokines.

The cytokine IL-15 might contribute to inflammatory processes, but also act as an inhibitor of apoptosis in different cell lines. Furthermore, it has been reported that islet cells express IL-15 after exposure to proinflammatory cytokines, which could indicate a defence reaction. We aimed in this study to investigate if IL-15 could influence cell death and/or functional impairment of rat pancreatic islets induced by in vitro exposure to a combination of cytokines (25 U/ml IL-1beta+1000 U/ml IFN-gamma+1000 U/ml TNF-alpha). The effect of IL-15 itself on the function of rat pancreatic islets was also studied. Isolated rat islets were exposed for 24 h to IL-15 at different concentrations in the presence or absence of the cytokine mixture. The cytokines caused a strong inhibition of glucose-stimulated insulin release and the glucose oxidation rates. IL-15 (0.1-10 ng/ml) could not prevent the functional suppression caused by these effects. The cytokine combination caused a decline in whole islet DNA content and a marked increase in non-viable cells analysed by propidium iodide (PI) and annexin V staining. However, there was no significant decrease in whole islet DNA content when IL-15 (0.1 or 1.0 ng/ml) was present together with the cytokine mixture. On the other hand, IL-15 failed to influence the increase in cell death after PI and annexin V staining. If anything, IL-15 alone had a slight stimulatory effect (glucose oxidation rate) on islet cells. In conclusion, we can not exclude that IL-15 might antagonize some cytokine mediated cell death in islet cells, however, IL-15 fails to counteract functional suppression induced by cytokines.