Cysteine and glutathione deficiency in AIDS patients: a rationale for the treatment with N-acetyl-cysteine.
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 SIVmac. 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-kappa B. 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-alpha (TNF-alpha), interleukin-2 receptor alpha-chain, and and beta 2-microglobulin. All the corresponding genes are associated with kappa-like enhancer sequences.(ABSTRACT TRUNCATED AT 250 WORDS)
Dröge
W
W
Division of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, BRD.
D000111:Acetylcysteine / Q000627:therapeutic use*; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D000596:Amino Acids / Q000097:blood; D003545:Cysteine / Q000172:deficiency*; D005978:Glutathione / Q000172:deficiency*; D006801:Humans; D013601:T-Lymphocytes / Q000378:metabolism
D000596:Amino Acids; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine