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J Appl Physiol 87: 438-443, 1999;
8750-7587/99 $5.00
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Vol. 87, Issue 1, 438-443, July 1999

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

James H. Roum1,2, Zea Borok1,4, Noel G. McElvaney1, George J. Grimes3, Allan D. Bokser3, Roland Buhl1, and Ronald G. Crystal1,5

1 Pulmonary Branch, National Heart, Lung, and Blood Institute, and 3 Pharmacy Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; 2 Division of Pulmonary and Critical Care Medicine, University of California Irvine Medical Center, Orange 92868; 4 Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Southern California, Los Angeles, California 90033; and 5 Division of Pulmonary Critical Care Medicine, The New York Hospital-Cornell Medical Center, New York, New York 10021

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 (O-2·) 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 O-2· 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.

antioxidant; bronchoalveolar lavage; neutrophil; respiratory epithelium; superoxide anion


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