title: 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)-gamma, and human immunodeficiency virus (HIV) type 1 infection in human macrophages were examined. Macrophages were infected with HIV-1 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-gamma (9-16 ng/mL) were detected. The addition of anti-IFN-gamma 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-gamma. The addition of anti-IFN-gamma 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.
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, 98104, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Akridge
authors.forename: S G
authors.initials: SG
authors.lastname: Reed
mesh_terms: D002450:Cell Communication; D002478:Cells, Cultured; D015536:Down-Regulation; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000821:virology; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology / Q000502:physiology
chemical_list: D018664:Interleukin-12; D007371:Interferon-gamma; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase