Weissman D, Ostrowski M, Daucher JA, Gantt K, Blauvelt A, Altman D, Shen L, Ehler L, Hoxie J, Grint P, Katz SI, Fauci AS; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
HIV replication is controlled by a delicate balance between HIV-enhancing and HIV-inhibitory cytokines and activation events. The pro-inflammatory cytokines are potent inducers of HIV replication in vitro and are thought to have similar activities in vivo. Interleukin (IL)-10 has anti-inflammatory and immunosuppressive activities, but also enhances CTL activity and FcR mediated endocytosis and killing. A phase 1 clinical trial of IL-10 in HIV-infected individuals with CD4+ T cell counts between 200 and 500/µL was undertaken to monitor safety, possible antiviral activity, and to determine effects on the endogenous cytokine network that may impact HIV replication in vivo. In addition, the effect of IL-10 on the recently described cofactors involved in HIV-1 entry into its target cells was analyzed. Subjects receiving a single infusion of IL-10 demonstrated no adverse effects and experienced a substantial, but transient decrease in their levels of plasma viremia. Pro-inflammatory cytokine production was inhibited after IL-10, but no decrease in antigen induced IL-2 secretion was observed. IL-10 also reduced expression on peripheral blood mononuclear cells of fusin (CXCR-4), the HIV fusion cofactor. Thus, IL-10 was well tolerated in HIV-infected individuals and transiently inhibited HIV replication through mechanisms that likely include alterations in the profile of endogenous cytokine environments involved in the regulation of HIV replication as well as modulation of HIV coreceptor expression.
Keywords: AEGIS, HIV, Viral Load, Interleukin-10, HIV-1, Virus Replication, Cytokines, Interleukin-2, CD4 Lymphocyte Count, HIV Infections, Receptors, CXCR4, Clinical Trials, Phase I, Interleukins, Anti-HIV Agents, Receptors, Interleukin-2, In Vitro, virology, AIDS
