Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis

James H. Roum, Zea Borok, Noel G. McElvaney, George J. Grimes, Allan D. Bokser, Roland Buhl, Ronald Crystal

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Abstract

Cystic fibrosis (CF) is characterized by accumulation of activated neutrophils and macrophages on the respiratory epithelial surface (RES); these cells release toxic oxidants, which contribute to the marked epithelial derangements seen in CF. These deleterious consequences are magnified, since reduced glutathione (GSH), an antioxidant present in high concentrations in normal respiratory epithelial lining fluid (ELF), is deficient in CF ELF. To evaluate the feasibility of increasing ELF GSH levels and enhancing RES antioxidant protection, GSH aerosol was delivered (600 mg twice daily for 3 days) to seven patients with CF. ELF total, reduced, and oxidized GSH increased (P < 0.05, all compared with before GSH therapy), suggesting adequate RES delivery and utilization of GSH. Phorbol 12-myristate 13- acetate-stimulated superoxide anion (O2/-·) release by ELF inflammatory cells decreased after GSH therapy (P < 0.002). This paralleled observations that GSH added in vitro to CF ELF inflammatory cells suppressed O2/-· release (P < 0.001). No adverse effects were noted during treatment. Together, these observations demonstrate the feasibility of using GSH aerosol to restore RES oxidant-antioxidant balance in CF and support the rationale for further clinical evaluation.

Original languageEnglish
Pages (from-to)438-443
Number of pages6
JournalJournal of Applied Physiology
Volume87
Issue number1
Publication statusPublished - 1 Jul 1999
Externally publishedYes

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Keywords

  • Antioxidant
  • Bronchoalveolar lavage
  • Neutrophil
  • Respiratory epithelium
  • Superoxide anion

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Roum, J. H., Borok, Z., McElvaney, N. G., Grimes, G. J., Bokser, A. D., Buhl, R., & Crystal, R. (1999). Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis. Journal of Applied Physiology, 87(1), 438-443.