Interleukin-10 inhibits antimicrobial activity against Leishmania major in murine macrophages

The stimulation of macrophages is of importance to the defense against intracellularly replicating microorganisms such as Leishmania. In this study the direct effect of recombinant interleukin-10 (IL-10) on the leishmanicidal effector functions of murine peritoneal or bone marrow derived macrophages was investigated. IL-10 almost completely inhibited the killing of intracellular leishmania at concentrations above 10 ng/ml. This inhibitory effect was independent of the stimulus used as the activation of macrophages by IFN-gamma and IL-7, recently shown to possess macrophage activating properties, were suppressed by IL-10. Kinetic experiments revealed that IL-10 must be present during the process of macrophage activation and that the leishmanicidal effector function of fully activated macrophages was not influenced. Furthermore, in the absence of exogenously added IL-10, the addition of neutralizing antibodies against IL-10 or IL-10-specific antisense phosphorothioate DNA-oligonucleotide led to an enhanced killing of parasites after stimulation with either IFN-gamma or IL-7. In accordance with this, IL-10 mRNA was readily detectable in murine macrophages by PCR with reverse transcribed mRNA. These results indicate that IL-10, which is endogenously produced by macrophages, acts as an autocrine deactivating factor supporting the survival of the parasite.