Modulation of endogenous IL-1βand IL-1 receptor antagonist results in opposing effects on HIV expression in chronically infected monocytic cells

Delia Goletti, Audrey L. Kinter, Elena C. Hardy, Guido Poli, Anthony S. Fauci

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Abstract

A proportion of HIV-infected individuals experience episodes of localized or systemic bacterial infections caused by Gram-negative bacteria. Many of the clinical side effects of these infections are associated with the production of proinflammatory cytokines, which are induced primarily by LPS, a constituent of the bacterial cell wall of Gram-negative bacteria. The present study examines the mechanisms involved in LPS-mediated induction of HIV expression in U1 cells, a promonocytic cell line chronically infected with HIV. Stimulation of U1 cells by LPS alone induced minimal levels of HIV expression, which was significantly enhanced by granulocyte-macrophage colony-stimulating factor (GM-CSF). Costimulation of U1 cells with LPS plus GM-CSF resulted in the accumulation of steady-state levels of HIV RNA; however, only a weak induction of HIV long terminal repeat-driven transcription, which was not associated with the activation of the cellular transcription factor nuclear factor-κB, was noted. Costimulation of cells with LPS plus GM-CSF induced the production of proinflammatory cytokines, IL-8, IL-1β and IL-6, but not TNF-α. IL-1 receptor antagonist (ra) inhibited LPS enhancement of HIV expression in GM-CSF-stimulated cells, suggesting that endogenous IL-1 was involved in LPS-mediated viral production. In this regard, anti-inflammatory cytokines inhibited LPS plus GM-CSF-stimulated HIV expression, and this effect closely correlated with inhibition of IL-1β release and, in particular, with up-regulation of endogenous IL-1 ra production. Thus, the balance between an endogenously produced viral inducer (IL-1β) and an inhibitor (IL-1ra) may represent an important pathway leading to modulation of HIV expression from monocytic cells.

Original languageEnglish
Pages (from-to)3501-3508
Number of pages8
JournalJournal of Immunology
Volume156
Issue number9
Publication statusPublished - May 1 1996

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ASJC Scopus subject areas

  • Immunology

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