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-gamma, 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-gamma levels were lower (P < 0.05) in patients than controls; this reduction was more pronounced for IFN-gamma 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-gamma, 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.