Document 0188
 DOCN  M95A0188
 TI    Increased levels of oxidized glutathione in CD4+ lymphocytes associated
       with disturbed intracellular redox balance in human immunodeficiency
       virus type 1 infection.
 DT    9510
 AU    Aukrust P; Svardal AM; Muller F; Lunden B; Berge RK; Ueland PM; Froland
       SS; Medical Department A, University of Oslo, National Hospital,;
       Norway.
 SO    Blood. 1995 Jul 1;86(1):258-67. Unique Identifier : AIDSLINE
       MED/95315545
 AB    We investigated the intracellular glutathione redox status in isolated
       lymphocyte subpopulations and monocytes in patients with human
       immunodeficiency virus type 1 (HIV-1) infection and 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 the most
       advanced clinical and immunologic disease were also characterized by an
       increase in levels of reduced glutathione in monocytes, suggesting that
       the glutathione redox cycle may be differentially regulated in CD4+
       lymphocytes and monocytes. We could not confirm previous reports
       suggesting 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.
 DE    Cysteine/DEFICIENCY  CD4-Positive T-Lymphocytes/*CHEMISTRY  Glutamic
       Acid/BLOOD  Glutamine/BLOOD  Glutathione/*BLOOD  Human  HIV
       Infections/*BLOOD  *HIV-1  Interleukin-2/BIOSYNTHESIS  Lymphocyte
       Subsets/CHEMISTRY  Oxidation-Reduction  Oxidative Stress  Support,
       Non-U.S. Gov't  Tumor Necrosis Factor/METABOLISM  JOURNAL ARTICLE

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