title: Interleukin-10 inhibits antimicrobial activity against Leishmania major in murine macrophages.
abstract: 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.
authors.affiliation: Institut für Klinische Mikrobiologie, Universität Erlangen-Nürnberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Vieth
authors.forename: A
authors.initials: A
authors.lastname: Will
authors.forename: K
authors.initials: K
authors.lastname: Schröppel
authors.forename: M
authors.initials: M
authors.lastname: Röllinghoff
authors.forename: A
authors.initials: A
authors.lastname: Gessner
mesh_terms: D000818:Animals; D000906:Antibodies; D001483:Base Sequence; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007371:Interferon-gamma / Q000502:physiology; D016753:Interleukin-10 / Q000502:physiology*; D015851:Interleukin-7 / Q000502:physiology; D018320:Leishmania major / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense
chemical_list: D000906:Antibodies; D015851:Interleukin-7; D016376:Oligonucleotides, Antisense; D016753:Interleukin-10; D007371:Interferon-gamma