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Cysteine and Glutathione Deficiency in AIDS Patients: A Rationale for the Treatment with N-Acetyl-Cysteine
Wulf Dröge

Division of Immunochemistry, Deutsches Krebsforschungs-zentrum, Heidelberg, BRD

Address of Corresponding Author

Pharmacology 1993;46:61-65 (DOI: 10.1159/000139029)

  Key Words

• Cysteine HIV infection
• Glutathione
• N-acetyl-cysteine
• NF-B

  Abstract

A series of clinical studies and laboratory investigations suggests that the acquired immunodeficiency syndrome (AIDS) may be the consequence of a virus-induced cysteine deficiency. HIV-infected persons at all stages of the disease were found to have decreased plasma cystine and cysteine concentrations and decreased intracellular glutathione levels. In rhesus macaques, cysteine levels decrease already within 1-2 weeks after infection with the closely related virus SIV_mac. HIV-infected persons and SIV-infected rhesus macaques have also, on the average, substantially increased plasma glutamate levels. Increased glutamate levels aggravate the cysteine deficiency by inhibiting the membrane transport of cystine. Even moderately elevated extracellular glutamate levels as they occur in HIV-infected persons cause a substantial decrease of intracellular cysteine levels. Clinical studies revealed that individual cystine and glutamate levels are correlated with the individual lymphocyte reactivity and T4+ cell counts but not T8+ cell counts. This phenomenon was demonstrated not only in HIV-infected persons but also in healthy human individuals. The cellular cysteine supply affects amongst others the intracellular glutathione level and IL-2-dependent proliferation of T cells and (inversely) also the activation of the transcription factor NF-kB. The cysteine deficiency of HIV-infected persons is, therefore, possibly responsible not only for the cellular dysfunction but also for the overexpression of tumor necrosis factor- (TNF-), interleukin-2 receptor -chain, and 2-microglobulin. All the corresponding genes are associated with B-like enhancer sequences. We have suggested that N-acetyl-cysteine may be considered for the replenishment of cysteine and glutathione levels in HIV-infected patients, since N-acetyl-cysteine is a well-established drug in clinical medicine with well-documented pharmacokinetics and safety.

Copyright © 1993 S. Karger AG, Basel

  Author Contacts

Wulf Dröge, Division of Immunochemistry, Deutsches Krebsforschungszentrum, D-W-6900 Heidelberg (FRG)

  Article Information

Received: March 6, 1992
Accepted: May 31, 1992
Published online: June 06, 2008
Number of Print Pages : 5