Decreased release of glutathione into the systemic circulation of patients with HIV infection.
Low glutathione (GSH) in patients with HIV infection could contribute to their immune deficiency since GSH plays an important role in the function of lymphocytes and sulphydryls decrease the expression of HIV in vitro. In order to gain more insight into the mechanisms responsible for the deranged sulphydryl homeostasis in HIV infection, the release of GSH into the circulation, an estimate of the systemic production of GSH, was determined using a pharmacokinetic approach. The basal plasma concentrations of free GSH (3.3 +/- 1.3 vs. 5.3 +/- 1.9 mumol L(-1)) and cysteine (7.7 +/- 2.6 vs. 13.4 +/- 4.9 mumol L(-1)) were significantly lower in eight HIV-infected patients than in eight controls. Upon infusion of GSH at a constant rate of 1 mumol min-1 kg-1, GSH in plasma reached a new plateau. The increment in plasma GSH was significantly larger in the HIV-infected patients than in the controls. The input of GSH into the circulation (12.9 +/- 5.7 vs. 30.1 +/- 11.7 mumol min-1; P < 0.01) and the clearance of GSH (25 +/- 7 vs. 35 +/- 7 mL min-1 kg-1) were significantly lower in patients with HIV-infection. During infusion of GSH the concentration of cysteine in peripheral blood mononuclear cells of the HIV-infected patients increased significantly. Nevertheless, intracellular GSH did not increase. Thus, the consumption of GSH is not increased in HIV infection. Rather, the present data suggest that GSH in patients with HIV infection is low because of a decreased systemic synthesis of GSH.
Helbling
B
B
Department of Clinical Pharmacology, University of Bern, Switzerland.
von Overbeck
J
J
Lauterburg
B H
BH
D000328:Adult; D000595:Amino Acid Sequence; D003545:Cysteine / Q000097:blood; D005260:Female; D005978:Glutathione / Q000096:biosynthesis / Q000097:blood*; D005998:Glycine / Q000097:blood; D015658:HIV Infections / Q000097:blood*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000821:virology; D008297:Male; D008715:Methionine / Q000097:blood; D008875:Middle Aged; D008969:Molecular Sequence Data; D013654:Taurine / Q000097:blood
D013654:Taurine; D008715:Methionine; D005978:Glutathione; D003545:Cysteine; D005998:Glycine