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

We investigated the intracellular glutathione redox status in isolated lymphocyte subpopulations and monocytes in patients with human immuno deficiency virus type 1 (HIV-1) infection acid in healthy controls. CD 4(+) lymphocytes from HIV-1-infected patients were primarily character ized by a substantial increase in oxidized glutathione levels and a co nsiderable decrease in the ratio of reduced to total glutathione, in m ost cases below 0.5 in patients with symptomatic HIV-1 infection, rath er than decreased levels of reduced glutathione. The increase in oxidi zed glutathione was strongly correlated with low numbers of CD4(+) lym phocytes in peripheral blood and impaired stimulated interleukin-2 pro duction and proliferation in peripheral blood mononuclear cells, which is compatible with an immunopathogenic role for these redox disturban ces. The HIV-1-infected patients with cysteine deficiency as a major c ause of disturbed glutathione homeostasis during HIV-1 infection. The demonstrated glutathione abnormalities were correlated with raised ser um levels of tumor necrosis factor alpha. These findings suggest that a therapeutical approach, which can restore the glutathione redox dysb alance in CD4(+) lymphocytes and decrease the inflammatory stress, may be worthwhile exploring in HIV-1 infection. (C) 1995 by The American Society of Hematology.