HIV alters plasma and M. tuberculosis-induced cytokine production in patients with tuberculosis

To test the hypothesis that HIV infection brings about an alteration in the immune response to tuberculosis (TB), mycobacterial antigen-induced production and plasma levels of the inflammatory cytokine interferon-gamma (IFN-gamma) and its regulatory cytokines interleukin-12 (IL-12), IL-18, and IL-10 were determined in patients infected dually with HIV and TB and compared with individuals with either disease and with healthy controls. Peripheral blood mononuclear cells (PBMCs) of TB patients with HIV infection produced lesser amounts of IFN-gamma and IL-12 compared with TB patients without HIV infection after in vitro stimulation with mycobacterial antigens. There was no difference in antigen-induced IL-18 production in TB patients with or without HIV infection. The in vivo cytokine pattern did not correlate with that seen in vitro. Higher levels of IFN-gamma, IL-12, and IL-18 were detected in the plasma of TB patients infected with HIV compared with TB patients without HIV infection. The presence of significantly higher plasma levels of proinflammatory cytokines suggests a greater degree of immune activation in individuals with HIV and TB, particularly those with low CD4 counts. In vitro IL-10 production by HIV-positive TB patients was similar to that of the HIV-negative TB group and higher than in HIV-positive individuals without TB, but the plasma levels were similar. HIV infection downregulates the in vitro Th1 cytokine response to TB and simultaneously increases systemic levels of these cytokines.