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Relationship of in vivo and ex vivo levels of TH1 and TH2 cytokines with viremia in HAART patients with and without opportunistic infections

TH1/TH2 cytokines' imbalance is critical to HIV‐1 progression and pathogenesis. Opportunistic infections‐related cytokine perturbations in the setting of highly active antiretroviral therapy (HAART) are unclear. The objective of this cross‐sectional study was to identify the relationship between TH1/TH2 cytokines and viremia in HAART patients with/without opportunistic infections. Sera from 17 HAART patients with and 43 without opportunistic infections, and 20 HIV‐seronegative controls were used to measure the levels of IL‐2, IFN‐γ, IL‐4, and IL‐10 proteins and mRNAs by ELISA and RNase protection assays, respectively. Ex vivo cytokine production by the CD4+/CD8+ T cells from four low and four high viremia patients randomly selected from non‐opportunistic infection group was also evaluated. Serum IL‐2 and IFN‐γ levels were lower (P < 0.05) in patients than controls; this reduction was more pronounced for IFN‐γ in non‐opportunistic infection patients. IL‐4 and IL‐10 were higher in patients than controls; this elevation was more remarkable in patients with opportunistic infections. Serum TH1/TH2 cytokine levels correlated with viremia. In vitro cytokine production assays showed that CD4+ T cells from low viremia patients mainly produced IL‐2 and IFN‐γ, CD8+ T cells from high viremia patients produced IL‐4, and both subsets comparably produced IL‐10 in patients with similar viremia. Positive correlations between sera/supernatant proteins and cellular mRNAs were also found statistically significant (P < 0.05). It was therefore concluded that in vivo TH1/TH2 cytokine levels in HAART patients and their ex vivo production by the CD4+/CD8+ T cells correlated with viremia and were also modulated by the presence of opportunistic infections in these patients. J. Med. Virol. 78:431–439, 2006. © 2006 Wiley‐Liss, Inc.