Sustained High Levels of Serum Interferon-γ During HIV-1 Infection: A Specific Trend Different from Other Cytokines

The expression levels of various cytokines increase with the progression of HIV-1 infection. However, the effects of antiretroviral therapy (ART) on serum cytokine levels have not been fully determined. In this study we measured serum cytokine levels of 35 HIV-1-infected Japanese adults. We first performed a cross-sectional study and observed that TNF-alpha, IL-6, IL-10, IL-18, and IL-7 levels all showed significant increases in those with advanced disease, and that this had a significant negative correlation with the CD4 cell count. However, IFN-gamma levels did not show this relationship. A longitudinal study in 18 HIV-1-infected patients with a CD4 cell count <350/mu L revealed that the introduction of ART reduced cytokine levels. Significant reductions of IL-7, IL-10, IFN-gamma, and IL-18 levels were observed on days 30, 60, 90, and 90 after the initiation of ART, respectively. These results indicate a discrepancy between cross-sectional and longitudinal studies of serum levels of IFN-gamma. To clarify this, we investigated serum IFN-gamma levels in each patient. In 5 of the 15 patients IFN-gamma levels did not decrease, even after ART initiation, and remained at 5 pg/mL or higher on day 120 after ART initiation. Higher IFN-gamma levels (>5 pg/mL) were also observed in 2 of 7 asymptomatic patients, and 2 of 11 patients who underwent ART for 1 year or longer. These data demonstrate that IFN-gamma levels in some patients increased and remained high even after the initiation of ART, which was a specific observation different from those of the other cytokines.