Enhanced production of tumor necrosis factor-alpha and interleukin-6 due to prolonged response to lipopolysaccharide in human macrophages infected invitro with human immunodeficiency virus-type 1

Elevated levels of circulating tumor necrosis factor (TNF)-alpha and interl eukin (IL)-6 have been detected in human immunodeficiency virus (HIV) type 1 infection. The overproduction of these cytokines could contribute to AIDS pathogenesis. Thus, the expression of TNF-alpha and IL-6 in human macropha ges infected with HIV-1 was investigated. HIV-1 infection, per se, did not induce any TNF-alpha or IL-6 production or cytokine-specific mRNA expressio n. In contrast, HIV-1 primed macrophages to a prolonged TNF-ol and IL-6 res ponse:to lipopolysaccharide (LPS) Stimulation with respect to uninfected ce lls. Time-course analysis and flow cytometry demonstrated that cytokine pro duction stopped at 6 h in uninfected macrophages but continued up to 24 h i n HIV-l-infected cells. RNA studies suggested :that,HIV-l interfered with l ate steps of cytokine synthesis. No modulation of membrane CD 14 was found to account for the enhanced response to LPS. Finally, the effect of HIV-1 o n cytokine response could not be abolished by the antiviral compound U75875 .