title: Potential role of interleukin-18 in the immunopathogenesis of AIDS: involvement in fratricidal killing of NK cells.
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.
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Innate Immunity, CHU-Sainte-Justine Research Center, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Iannello
authors.forename: Suzanne
authors.initials: S
authors.lastname: Samarani
authors.forename: Olfa
authors.initials: O
authors.lastname: Debbeche
authors.forename: Rasheed
authors.initials: R
authors.lastname: Ahmad
authors.forename: Mohamed-Rachid
authors.initials: MR
authors.lastname: Boulassel
authors.forename: Cécile
authors.initials: C
authors.lastname: Tremblay
authors.forename: Emil
authors.initials: E
authors.lastname: Toma
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmad