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Journal of Clinical Immunology

, Volume 18, Issue 2, pp 124–131 | Cite as

Induction of HIV-1 Replication by Type 1-Like Cytokines, Interleukin (IL)-12 and IL-15: Effect on Viral Transcriptional Activation, Cellular Proliferation, and Endogenous Cytokine Production

  • Lena Al-Harthi
  • Kenneth A. Roebuck
  • Alan Landay
Article

Abstract

Cytokine dysregulation is evident in HIV-1 infection and it may play an important role in HIV-1 pathogenesis. Administration of T helper cytokines potentially may restore the functional abnormalities to the HIV-1 immune response. Type 1-like cytokines, IL-2, IL-12, and IL-15, are candidates for immune-based therapy for HIV. Given their potential therapeutic use, we determined the effects of IL-2, IL-12, and IL-15 on HIV-1 replication in both primary blood mononuclear cells (PBMC) and the T-cell line, Kit 225-K6. We demonstrate that both IL-2 and IL-12 induce a similar level of HIV-1 replication (9- and 11-fold, respectively) in mitogen-stimulated PBMC. The effect of IL-2 plateaued by day 6, while that of IL-12 continued to increase HIV-1 expression. IL-15 induced a 2.5-fold increase in HIV-1 expression that remained at the same level through day 6. In Kit 225-K6, an IL-2-dependent T cell line, IL-12 and IL-15 enhanced HIV-1 replication by 5- and 3.5-fold over IL-2-treated cultures, respectively. IL-2-, IL-12-, and IL-15-mediated induction of HIV was independent of direct HIV-1 LTR activation, since none of the cytokines induced LTR activity from transfected reporter gene constructs. The cytokine-mediated induction of HIV-1 expression was also independent of cellular proliferation. In PBMC, the IL-12-mediated effect was partially mediated by endogenous cytokine production of IL-1β and IL-7, whereas in Kit 225-K6, TNFα, INFγ, IL-1β, and IL-7 did not contribute significantly to the IL-12-mediated effect. IL-15 effect on HIV-1 in PBMC was independent of endogenous cytokine production. However, in Kit 225-K6, neutralizing antibodies to IL-7 had a significant effect on HIV-1 expression. These data suggest that IL-2, IL-12, and IL-15 increase HIV-1 replication predominantly through a posttranscriptional mechanism that may be enhanced by endogenous cytokine production.

Interleukin (IL)-12 IL-15 human immunodeficiency virus AIDS immune-based therapy 

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Copyright information

© Plenum Publishing Corporation 1998

Authors and Affiliations

  • Lena Al-Harthi
    • 1
  • Kenneth A. Roebuck
    • 1
  • Alan Landay
    • 1
  1. 1.Department of Immunology/MicrobiologyLuke's Medical CenterChicago

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