IL-10 up-regulates nitric oxide (NO) synthesis by lipopolysaccharide (LPS)-activated macrophages: improved control ofTrypanosoma cruziinfection

Abstract

We examined the effects of IL‐10 on tumour necrosis factor‐alpha (TNF‐α) and NO production by LPS‐activated macrophages and on the ability of these cells to control Trypanosoma cruzi infection. We first observed that the addition of rIL‐10 to macrophages of the J774 cell line decreased their synthesis of TNF‐α but increased their release of NO in a dose‐dependent manner. In parallel, treatment of J774 cells with rIL‐10 resulted in a better control of T. cruzi infection involving up‐regulation of NO synthesis, as it was not observed in presence of N‐nitro‐ L‐arginine methyl ester ( L‐NAME), a competitive inhibitor of NO synthase. The enhancing effect of rIL‐10 on NO production was not observed on peritoneal macrophages from wild‐type C57Bl/6 mice, but well on macrophages from IL‐10 knock‐out mice. The control of NO production by endogenous IL‐10 was confirmed by the demonstration that neutralization of IL‐10 secreted by LPS‐activated macrophages from wild‐type mice inhibited their production of NO and, in parallel, their ability to control T. cruzi infection. Taken together, these data demonstrate that both exogenous and endogenous IL‐10 up‐regulate the production of NO by LPS‐activated macrophages and improve thereby their ability to clear T. cruzi infection.