HIV-1 infection of macrophages promotes long-term survival and sustained release of interleukins 1 alpha and 6.
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.
Berman
M A
MA
Department of Medicine, California College of Medicine, University of California, Irvine 92717.
Zaldivar
F
F
Imfeld
K L
KL
Kenney
J S
JS
Sandborg
C I
CI
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
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha