Interleukin-10 and interleukin-4 inhibit intracellular killing of Leishmania infantum and Leishmania major by human macrophages by decreasing nitric oxide generation.
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 (M phi). As with L. major, intracellular killing of L. infantum by human M phi was obtained following ligation of surface CD23 or cell treatment with interferon-gamma (IFN-gamma). This leishmanicidal activity required nitric oxide (NO) generation by activated M phi, 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-gamma decreased L. infantum and L. major killing by infected M phi. IL-10 was more potent than IL-4 in inhibiting the leishmanicidal activity of human M phi. Inhibition of Leishmania killing by IL-4 and IL-10 correlated with decreased NO generation from M phi, and was reversed when exogenous NO was added to cell cultures. Therefore, IL-10 and IL-4 down-regulate leishmanicidal activity of human M phi, in part by inhibiting NO generation by these cells.
Vouldoukis
I
I
INSERM U318, Pitié-Salpêtrière Hospital, Paris, France.
Bécherel
P A
PA
Riveros-Moreno
V
V
Arock
M
M
da Silva
O
O
Debré
P
P
Mazier
D
D
Mossalayi
M D
MD
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000276:immunology / Q000469:parasitology; D018314:Leishmania infantum / Q000187:drug effects / Q000276:immunology*; D018320:Leishmania major / Q000187:drug effects / Q000276:immunology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology
D016753:Interleukin-10; D015847:Interleukin-4; D009569:Nitric Oxide