The effect of cytokines and pharmacologic agents on chronic HIV infection

G. Poli, A. S. Fauci

Research output: Contribution to journalArticle

Abstract

The ability of the human immunodeficiency virus (HIV) to replicate in CD4+ T lymphocytes and mononuclear phagocytes (MP) is strongly influenced by immunoregulatory cytokines. In the T cell system, interleukin-2 (IL-2) provides a mitogenic signal leading to both cell proliferation and virus replication. Among other HIV-inductive cytokines, only tumor necrosis factor- α or -β (TNF-α/-β) have been shown thus far to trigger virus expression both in T cells and MP. The mechanism of action of TNF involves the activation of the cellular transcription factor NF-kB which binds to specific consensus sequences present in the enhancer region of the HIV proviral LTR. In addition, several other cytokines (including colony stimulating factors, IL-1, IL-3, and IL-6) have demonstrated upregulatory effects on HIV production in MP, whereas nonimmune interferons (INF-α/-β) have been shown to suppress HIV replication in T cells and MP by acting at different phases in the virus life cycle. Finally, cytokines such as TGF-β, IFN-γ, and IL-4 have demonstrated either upregulatory or suppressive effects on virus expression depending on the experimental conditions. This scenario indicates that HIV expression is under the control of a complex network of immunoregulatory cytokines, in addition to its own endogenous regulatory proteins, suggesting that new pharmacologic strategies may be aimed at either mimicking or interrupting cytokine-dependent virus expression. In this regard, a number of different physiologic and pharmacologic agents capable of interfering with cytokine-mediated events, including glucocorticoids, anti- oxidants, such as N-Acetyl-L-Cysteine (NAC), and retinoic acid (RA) have already been shown to profoundly affect HIV replication in vitro.

Original languageEnglish
Pages (from-to)191-197
Number of pages7
JournalAIDS Research and Human Retroviruses
Volume8
Issue number2
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Immunology
  • Virology

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