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

Background: A key factor leading to impaired immunity in HIV infection is a n alteration of the pattern of cytokine response, although its precise natu re remains controversial, particularly the in vivo influence of HIV on inte rleukin (IL)-12 synthesis. Design: A cross-sectional study in 73 HIV-infected persons (28 of them rece iving highly active antiretroviral therapy) acid 18 HIV-seronegative health y donors. Methods: The frequency of monocytes/macrophages (M/M) synthesizing IL-12, I L-10 and tumour necrosis factor alpha (TNF-alpha) was determined in periphe ral blood mononuclear cells. The cells were cultured in medium or were stim ulated with lipopolysaccharide; proportions of CD64 M/M producing IL-12, TN F-alpha or IL-10 was determined by cytofluorometric analysis. The influence of exogenous interferon gamma (IFN-gamma), IL-10 or IL-15 on IL-12 synthes is was tested. Results: Chronic HIV disease is associated with increased priming of M/M fo r IL-12 (involving both p40 and p70 molecules) and TNF-alpha synthesis; thi s was associated with cosynthesis of both cytokines by a fraction of M/M. P riming for IL-12 was physiologically enhanced by IFN-gamma 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 co rrelation between IL-10-producing M/M and viral load. IL-12 production was not correlated with viral load but was increased following antiretroviral t herapy. Following LPS stimulation, IL-12 and TNF-alpha responses were not a ltered 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. (C) 2001 Lippincott Williams & Wilkin s.