INCREASED LEVELS OF OXIDIZED GLUTATHIONE IN CD4(+) LYMPHOCYTES ASSOCIATED WITH DISTURBED INTRACELLULAR REDOX BALANCE IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION

We investigated the intracellular glutathione redox status in isolated lymphocyte subpopulations and monocytes in patients with human immunodeficiency virus type 1 (HIV-1) infection acid in healthy controls. CD4(+) lymphocytes from HIV-1-infected patients were primarily characterized by a substantial increase in oxidized glutathione levels and a considerable decrease in the ratio of reduced to total glutathione, in most cases below 0.5 in patients with symptomatic HIV-1 infection, rather than decreased levels of reduced glutathione. The increase in oxidized glutathione was strongly correlated with low numbers of CD4(+) lymphocytes in peripheral blood and impaired stimulated interleukin-2 production and proliferation in peripheral blood mononuclear cells, which is compatible with an immunopathogenic role for these redox disturbances. The HIV-1-infected patients with cysteine deficiency as a major cause of disturbed glutathione homeostasis during HIV-1 infection. The demonstrated glutathione abnormalities were correlated with raised serum levels of tumor necrosis factor alpha. These findings suggest that a therapeutical approach, which can restore the glutathione redox dysbalance in CD4(+) lymphocytes and decrease the inflammatory stress, may be worthwhile exploring in HIV-1 infection. (C) 1995 by The American Society of Hematology.