Significance of glutathione in lung disease and implications for therapy.

Glutathione is a tripeptide that contains an important thiol (sulfhydryl) group within the central cysteine amino acid. Glutathione is involved in numerous vital processes where the reducing potential of the thiol is used. Several lung disorders are believed to be characterized by an increase in alveolar oxidant burden, potentially depleting alveolar and lung glutathione. Low glutathione has been linked to abnormalities in the lung surfactant system and the interaction between glutathione and antiproteases in the epithelial lining fluid of patients. Normal levels of intracellular glutathione may exert a critical negative control on the elaboration of proinflammatory cytokines. The increase of intracellular reactive oxygen species is believed to correlate with the activation of NF-kappa B, a transcription activator linked to the elaboration of several cytokines. There is now sufficient data to strongly implicate free radical injury in the genesis and maintenance of several lung disorders in humans. This information is substantial and will help the development of clinical studies examining a variety of inflammatory lung disorders.