IL-10 synergizes with multiple cytokines in enhancing HIV production in cells of monocytic lineage.
Several cytokines, whose expression is increased in human immunodeficiency virus (HIV)-infected individuals, can enhance virus replication in CD4+ T lymphocytes and mononuclear phagocytes (MP). We have previously reported that interleukin (IL)-10 inhibited HIV replication in acutely infected monocyte-derived macrophages (MDM) at concentrations that completely blocked the production of endogenous tumor necrosis factor-alpha (TNF-alpha) and IL-6 from infected cells. In the present study, lower concentrations of IL-10, which were unable to completely suppress endogenous cytokines, paradoxically enhanced HIV replication in MDM induced by other cytokines. This synergistic induction of HIV expression by IL-10 in combination with TNF-alpha, IL-6, and other cytokines was also observed in the chronically infected promonocytic cell line, U1. The enhancing effect of IL-10 was correlated with an increase in HIV mRNA accumulation and potentiation of phorbol ester-induced long terminal repeat-driven transcription that was independent of the NF-kappa B and Sp1 transcription factors. Thus, IL-10 is a cytokine capable of exerting complex regulatory effects on HIV expression in MP as a function of its own concentration and of the presence of other HIV regulatory cytokines.
Weissman
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Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Poli
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Fauci
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AS
D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004357:Drug Synergism; D006678:HIV / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000821:virology*; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10