title: HIV-1 causes an imbalance in the production of interleukin-18 and its natural antagonist in HIV-infected individuals: implications for enhanced viral replication.
abstract: BACKGROUND
  Concentrations of interleukin (IL)-18 increase in the circulation of human immunodeficiency virus (HIV)-infected persons. However, nothing is known concerning the regulation of IL-18-binding protein (IL-18BP), which neutralizes IL-18 in vivo. This issue is addressed in the present study.
  
  
  METHODS
  Serum samples obtained from healthy subjects and HIV-infected patients were analyzed by enzyme-linked immunosorbent assay to determine their IL-18 and IL-18BP contents. Human monocyte-derived macrophages (MDMs) were infected in vitro with HIV type 1 (HIV-1), and the production of these 2 cytokines by these cells was measured. Finally, we determined the effect of IL-18 on HIV-1 replication in human cells.
  
  
  RESULTS
  In contrast to IL-18 levels, IL-18BP levels decreased in the serum of HIV-infected patients. This decrease resulted in enhanced levels of free IL-18 in the serum of such patients. The infection increased production of IL-18 but decreased that of IL-18BP in MDMs. IL-10 and transforming growth factor-beta, concentrations of which are increased in HIV-infected persons, also decreased production of IL-18BP by human MDMs. Finally, recombinant human IL-18 enhanced HIV-1 replication in human CD4(+) T cells.
  
  
  CONCLUSIONS
  Production of IL-18 and its antagonist becomes imbalanced in HIV-1-infected persons. The infection and the cytokine milieu play a role in this decreased production. The increased biological activities of IL-18 may enhance viral replication in human CD4(+) T cells.
authors.affiliation: Laboratory of Innate Immunity, Centre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, Quebec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Iannello
authors.forename: Mohamed-Rachid
authors.initials: MR
authors.lastname: Boulassel
authors.forename: Suzanne
authors.initials: S
authors.lastname: Samarani
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
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D015658:HIV Infections / Q000097:blood* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000097:blood; D016753:Interleukin-10 / Q000378:metabolism; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014779:Virus Replication / Q000276:immunology / Q000502:physiology*
chemical_list: C508609:IL10 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D016212:Transforming Growth Factor beta; C118370:interleukin-18 binding protein; D016753:Interleukin-10