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

Eur J Immunol. 1997 Apr;27(4):860-5. doi: 10.1002/eji.1830270409.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytotoxicity, Immunologic* / drug effects
  • Down-Regulation / immunology
  • Humans
  • Interleukin-10 / pharmacology*
  • Interleukin-4 / pharmacology*
  • Intracellular Fluid / immunology
  • Intracellular Fluid / parasitology
  • Leishmania infantum / drug effects
  • Leishmania infantum / immunology*
  • Leishmania major / drug effects
  • Leishmania major / immunology*
  • Macrophage Activation / drug effects
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide / physiology


  • Interleukin-10
  • Interleukin-4
  • Nitric Oxide