title: HIV-1 infection of macrophages promotes long-term survival and sustained release of interleukins 1 alpha 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-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 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-1 alpha, IL-1 beta, and IL-6 bioactivity by adherent 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 culture. High levels of bioactive IL-1 beta were released only up to 72 hr following infection, although intracellular IL-1 beta was detectable for at least 3 weeks. No TNF-alpha 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-1 alpha 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.
authors.affiliation: Department of Medicine, California College of Medicine, University of California, Irvine 92717.
authors.forename: M A
authors.initials: MA
authors.lastname: Berman
authors.forename: F
authors.initials: F
authors.lastname: Zaldivar
authors.forename: K L
authors.initials: KL
authors.lastname: Imfeld
authors.forename: J S
authors.initials: JS
authors.lastname: Kenney
authors.forename: C I
authors.initials: CI
authors.lastname: Sandborg
mesh_terms: D002470:Cell Survival; D015658:HIV Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D007700:Kinetics; D008264:Macrophages / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013601:T-Lymphocytes / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha