Increased priming for interleukin-12 and tumour necrosis factor α in CD64 monocytes in HIV infection: modulation by cytokines and therapy

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Abstract
Background A key factor leading to impaired immunity in HIV infection is an alteration of the pattern of cytokine response, although its precise nature remains controversial, particularly the in vivo influence of HIV on interleukin (IL)-12 synthesis. Design A cross-sectional study in 73 HIV-infected persons (28 of them receiving highly active antiretroviral therapy) and 18 HIV-seronegative healthy donors. Methods The frequency of monocytes/macrophages (M/M) synthesizing IL-12, IL-10 and tumour necrosis factor α (TNF-α) was determined in peripheral blood mononuclear cells. The cells were cultured in medium or were stimulated with lipopolysaccharide; proportions of CD64 M/M producing IL-12, TNF-α or IL-10 was determined by cytofluorometric analysis. The influence of exogenous interferon γ (IFN-γ), IL-10 or IL-15 on IL-12 synthesis was tested. Results Chronic HIV disease is associated with increased priming of M/M for IL-12 (involving both p40 and p70 molecules) and TNF-α synthesis; this was associated with cosynthesis of both cytokines by a fraction of M/M. Priming for IL-12 was physiologically enhanced by IFN-γ and decreased by IL-10; IL-15 had no effect. The proportion of IL-10-producing CD64 M/M was not altered in patients compared with controls but there was an inverse correlation between IL-10-producing M/M and viral load. IL-12 production was not correlated with viral load but was increased following antiretroviral therapy. Following LPS stimulation, IL-12 and TNF-α responses were not altered in HIV-positive patients; however, the IL-10 response was decreased but restored by antiretroviral therapy. Conclusion These observations argue for a preserved intrinsic CD64 M/M of IL-12 production in HIV pathogenesis.

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