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.
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
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Laffranchi
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Spinas
D000818:Animals; D005260:Female; D007328:Insulin / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins
D007328:Insulin; D007375:Interleukin-1; D009573:Nitrites; D011994:Recombinant Proteins; D016753:Interleukin-10; D009569:Nitric Oxide