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    J Virol. 2009 Jun;83(12):5999-6010. Epub 2009 Apr 1.

    Potential role of interleukin-18 in the immunopathogenesis of AIDS: involvement in fratricidal killing of NK cells.

    Iannello A, Samarani S, Debbeche O, Ahmad R, Boulassel MR, Tremblay C, Toma E, Routy JP, Ahmad A.

    Source

    Department of Microbiology and Immunology, Laboratory of Innate Immunity, CHU-Sainte-Justine Research Center, University of Montreal, Montreal, Quebec, Canada.

    Abstract

    We had shown earlier that the concentrations of circulating interleukin-18 (IL-18) are increased significantly in human immunodeficiency virus (HIV)-infected persons compared to HIV-seronegative healthy subjects. In the present study, we investigated the consequences of these elevated levels of IL-18 on natural killer (NK) cells and the immunopathogenesis of AIDS. We show here an inverse correlation between IL-18 concentrations and absolute numbers of various subsets of NK cells in infected persons. Recombinant human IL-18 caused increased death of a human NK cell line, as well as of primary human NK cells in vitro. The IL-18-mediated cell death was dependent upon Fas-FasL interactions and tumor necrosis factor alpha. IL-18 induced the expression of FasL on NK cells, increased the transcription from the human FasL promoter, reduced the expression of Bcl-X(L) in NK cells, and increased their sensitivity to FasL-mediated cell death. These results suggest that increased IL-18 concentrations present in the circulation of HIV-infected persons contribute to the immunopathogenesis of AIDS by altering NK cell homeostasis.

    PMID:
    19339355
    [PubMed - indexed for MEDLINE]
    PMCID: PMC2687374
    Free PMC Article

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