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.