Interleukin-13 counteracts suppression induced by interleukin-1beta of glucose metabolism but not of insulin secretion in rat pancreatic islets.

The cytokine interleukin-1beta (IL-1beta) has been postulated to be involved in beta-cell destruction in IDDM. It has also been suggested that this action by IL-1beta is mediated by nitric oxide (NO) generation. Recently it has been reported that Th2-cell promoting cytokines e.g. interleukin-4 (IL-4) and interleukin-13 (IL-13) can reduce NO formation from activated macrophaghes after cytokine activation. In the present study we examined the effect of IL-13 on IL-1beta suppression of islet function. For this purpose rat pancreatic islets were cultured in medium RPMI 1640 + 10% fetal calf serum and exposed for 42 h to human IL-13 (0. 0.1, 1 and 10 ng/ml) in the presence or absence of human IL-1beta (25 U/ml) during the last 24 h of culture. IL-13 alone did not affect any islet functions during prolonged exposure. The highest concentration of IL-13 counteracted IL-1beta suppression of islet glucose oxidation, but not insulin release. Moreover, IL-13 failed to reduce IL-1beta stimulated NO production, as measured by medium nitrite levels. Acute exposure to IL-13 caused a slight stimulation of islet insulin secretion. When IL-4 (10 ng/ml) was combined with IL-13 no synergistic action of the two cytokines was observed in the counteraction of IL-1beta mediated changes. In conclusion, the present study showed that IL-13 could partially prevent IL-1beta induced inhibition of the glucose metabolism, and this effect appeared to be unrelated to NO levels. So far it has not been possible to demonstrate in vitro that Th2-cell promoting cytokines such as IL-4 and IL-13 can effectively reduce cytokine-induced NO from islet cells, as has been reported for macrophages. However, it cannot be excluded that Th2-cell promoting cytokines can be effective in reducing a Th1-cell mediated anti-beta-cell response in vivo.