Interleukin‐10 and interleukin‐4 inhibit intracellular killing of Leishmania infantum and Leishmania major by human macrophages by decreasing nitric oxide generation

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Abstract
The host response to Leishmania infection is regulated by a specific pattern of local cytokine production. We investigated the effect of interleukin (IL)-10 and IL-4 on the leishmanicidal activity of human macrophages (Mϕ). As with L. major, intracellular killing of L. infantum by human Mϕ was obtained following ligation of surface CD23 or cell treatment with Interferon-γ (IFN-γ). This leishmanicidal activity required nitric oxide (NO) generation by activated Mϕ, and it was partially mimicked by cell treatment with chemical NO donors. Addition of recombinant human IL-10 or IL-4 to CD23 mAb or IFN-γ decreased L. infantum and L. major killing by infected Mϕ. IL-10 was more potent than IL-4 in inhibiting the leishmanicidal activity of human Mϕ. Inhibition of Leishmania killing by IL-4 and IL-10 correlated with decreased NO generation from Mϕ, and was reversed when exogenous NO was added to cell cultures. Therefore, IL-10 and IL-4 down-regulate leishmanicidal activity of human Mϕ, in part by inhibiting NO generation by these cells.