Interleukin-10 suppresses human immunodeficiency virus-1 replication in vitro in cells of the monocyte/macrophage lineage

M. Wayne Saville, Kazayuki Taga, Andrea Foli, Samuel Broder, Giovanna Tosato, Robert Yarchoan

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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 (IC 50) 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-1β, IL-6, or tumor necrosis factor-α 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 or 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.

Original languageEnglish
Pages (from-to)3591-3599
Number of pages9
Issue number12
Publication statusPublished - Jun 15 1994

ASJC Scopus subject areas

  • Hematology

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