HIV-1 Infection of Macrophages Promotes Long-Term Survival and Sustained Release of Interleukins lα and 6

Abstract

HIV infection of macrophages in vivo may result in activation of monokine genes and cause persistent release of immunomodulatory and inflammatory cytokines. Studies that have examined cytokine (IL-1,IL-6, and TNF-α) 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 preparations derived from the H9 tumor cell line, partial purification of virus particles is essential. Infectious HIV-1 induces the release of high levels of IL-1α, IL-1β, and IL-6 bioactivity by adherent PBMCs in the first 3 days following in vitro infection, but only IL-1α and IL-6 continue to be released over several weeks of culture. High levels of bioactive IL-1β were released only up to 72 hr following infection, although intracellular IL-1β was detectable for at least 3 weeks. No TNF-α bioactivity or immunoreactive protein was detectable at >48 hr in HIV-infected cultures. This time course of monokine release was dependent on the number of infectious particles added to PBMC cultures. In long-term cultures (>1 month) HIV infection was found to promote the viability of macrophages. The finding of sustained release of IL-1α and IL-6 by infected macrophages, without additional stimulation, suggests that these mediators are released by HIV-1-infected macrophages in AIDS patients, where they may interfere with proper immune regulation.