Interleukin-12 Decreases Human Immunodeficiency Virus Type 1 Replication in Human Macrophage Cultures Reconstituted with Autologous Peripheral Blood Mononuclear Cells

Abstract

In vitro interactions between interleukin (IL)-12, interferon (IFN)-γ, and human immunodeficiency virus (HIV) type 1 infection in human macrophages were examined. Macrophages were infected with HIV-l and cocultured with autologous monocyte-depleted peripheral blood mononuclear cells (PBMC). The addition of autologous PBMC to HIV-1-infected macrophages resulted in an expansive increase in reverse transcriptase (RT) activity; however, when both autologous PBMC and IL-12 were added, RT activity decreased (75%–90%) and high levels of IFN-γ (9–16 ng/mL)were detected. The addition of anti-IFN-γ antibodies blocked the IL-12-induced decrease in RT activity. Surprisingly, exogenous IL-12 added to HIV-infected macrophage cultures without autologous lymphocytes resulted in a 50%–60% reduction in RT activity and no detectable increase in IFN-γ. The addition of anti-IFN-γ did not inhibit this IL-12-mediated effect. These results suggest that IL-12 is capable of indirectly down-regulating HIV proliferation in macrophage cultures reconstituted with autologous PBMC and of directly suppressing HIV replication in purified macrophage cultures.