Interleukin 10 inhibits insulin release from and nitric oxide production in rat pancreatic islets.

Interleukin 10 was found to prevent cytokine-induced nitric oxide production in murine macrophages. Because, in rat islets, interleukin 1 beta induces beta-cell dysfunction, mainly due to overproduction of nitric oxide, we studied if this effect could be counteracted by interleukin 10. Rat pancreatic islets were cultured for 24 h in the presence or absence of 0.02-20 ng/ml recombinant human interleukin 10. Interleukin 10 dose-dependently inhibited insulin secretion with maximal inhibition (27 +/- 4%, p < 0.05) at 2 ng/ml without impairment of islet cell viability. However, incubation of pancreatic islets with interleukin 10 resulted in a 61.5% decrease of nitric oxide production. Co-incubation of islets with interleukin 10 (2 ng/ml) and recombinant human interleukin 1 beta (0.15 ng/ml) resulted in a more pronounced suppression of basal insulin release than with interleukin 1 beta alone (55 +/- 3.6% vs 44 +/- 3.6% with interleukin 1 beta alone, p < 0.05) but did not reduce interleukin 1 beta-stimulated NO production or reverse the effect of interleukin 1 beta on cell viability. Thus, in pancreatic islets interleukin 10 is not capable of counteracting the interleukin 1 beta induced beta-cell dysfunction, but rather enhances the inhibitory effect of interleukin 1 beta by a different mechanism.