title: Interleukin-10 suppresses human immunodeficiency virus-1 replication in vitro in cells of the monocyte/macrophage lineage.
abstract: The cytokine interleukin-10 (IL-10) has been implicated in the pathogenesis of a number of disease states, including Epstein-Barr virus and human immunodeficiency virus (HIV-1) infections. In the acquired immunodeficiency syndrome (AIDS), it has been suggested that IL-10 may have a deleterious effect by suppressing cell-mediated immunity. However, there are few data on its direct effects on HIV-1 replication. In the present study, we have found that recombinant human IL-10 (rhIL-10), present during days 0 through 2, potently inhibits HIV production in elutriated monocyte/macrophage (M/M) cultures with a 50% inhibitory concentration (IC50) of approximately 0.03 U/mL. This effect did not appear to be caused by toxicity to M/M because there was no change in cell viability, ability to phagocytose latex beads, or protein synthesis as measured by [3H]-leucine incorporation, at doses of rhIL-10 that inhibit viral replication. In addition, lipopolysaccharide-induced production of IL-1 beta, IL-6, or tumor necrosis factor-alpha was not affected at these doses, nor were human mononuclear cell proliferative responses to phytohemagglutinin, OKT3 antibody, or tetanus toxoid. HIV-1 replication was similarly decreased by rhIL-10 in the monocytoid line U937 without signs of cellular toxicity. However, these effects required much higher concentrations of rhIL-10, and viral production was only partially suppressed. rhIL-10 also slightly inhibited HIV-induced cytopathicity in ATH-8, a tetanus toxoid-specific, retrovirally immortalized T-cell line, but had no effect on HIV replication in the H9 and MOLT-4 T cell lines. Thus, rhIL-10 appears to inhibit HIV replication predominantly in cells of the M/M lineage. This effect may serve to reduce viral production in patients with AIDS. However, additional studies will be needed to more precisely define its physiologic role in this disease.
authors.affiliation: Retroviral Diseases Section, National Cancer Institute, Bethesda, MD 20892.
authors.forename: M W
authors.initials: MW
authors.lastname: Saville
authors.forename: K
authors.initials: K
authors.lastname: Taga
authors.forename: A
authors.initials: A
authors.lastname: Foli
authors.forename: S
authors.initials: S
authors.lastname: Broder
authors.forename: G
authors.initials: G
authors.lastname: Tosato
authors.forename: R
authors.initials: R
authors.lastname: Yarchoan
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology; D002478:Cells, Cultured; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D009000:Monocytes / Q000187:drug effects / Q000382:microbiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D011994:Recombinant Proteins; D016753:Interleukin-10