IL-10 SYNERGIZES WITH MULTIPLE CYTOKINES IN ENHANCING HIV PRODUCTION IN CELLS OF MONOCYTIC LINEAGE

Several cytokines, whose expression is increased in human immunodeficiency virus (HIV)-infected individuals, can enhance virus replication in CD4(+) T lymphocytes and mononuclear phagocytes (MP). We have previously reported that interleukin (IL)-10 inhibited HIV replication in acutely infected monocyte-derived macrophages (MDM) at concentrations that completely blocked the production of endogenous tumor necrosis factor-alpha (TNF-alpha) and IL-6 from infected cells. In the present study, lower concentrations of IL-10, which were unable to completely suppress endogenous cytokines, paradoxically enhanced HIV replication in MDM induced by other cytokines. This synergistic induction of HIV expression by IL-10 in combination with TNF-alpha, IL-6, and other cytokines was also observed in the chronically infected promonocytic cell line, U1. The enhancing effect of IL-10 was correlated with an increase in HIV mRNA accumulation and potentiation of phorbol ester-induced long terminal repeat-driven transcription that was independent of the NF-kappa B and Spl transcription factors. Thus, IL-10 is a cytokine capable of exerting complex regulatory effects on HIV expression in MP as a function of its own concentration and of the presence of other HIV regulatory cytokines.