HIV-1 INFECTION OF MACROPHAGES PROMOTES LONG-TERM SURVIVAL AND SUSTAINED-RELEASE OF INTERLEUKIN-1-ALPHA AND INTERLEUKIN-6

HN infection of macrophages in vivo may result in activation of monoki ne genes and cause persistent release of immunomodulatory and inflamma tory cytokines. Studies that have examined cytokine (IL-1, IL-6, and T NF-alpha) activation by in vitro infection of normal peripheral blood mononuclear cells (PBMCs) with HIV-1 have produced conflicting results . The present study shows that for monokine induction by HIV-1-IIIB pr eparations derived from the H9 tumor cell line, partial purification o f virus particles is essential. Infectious HIV-1 induces the release o f high levels of IL-1 alpha, IL-1 beta, and IL-6 bioactivity by adhere nt PBMCs in the first 3 days following in vitro infection, but only IL -1 alpha and IL-6 continue to be released over several weeks of cultur e. High levels of bioactive IL-1 beta were released only up to 72 hr f ollowing infection, although intracellular IL-1 beta was detectable fo r at least 3 weeks. No TNF-alpha bioactivity or immunoreactive protein was detectable at >48 hr in HIV-infected cultures. This time course o f monokine release was dependent on the number of infectious particles added to PBMC cultures. In long-term cultures (>1 month) HIV infectio n was found to promote the viability of macrophages. The finding of su stained release of IL-1 alpha and IL-6 by infected macrophages, withou t additional stimulation, suggests that these mediators are released b y HIV-1-infected macrophages in BIDS patients, where they may interfer e with proper immune regulation.