cell-derived oxidants in cystic fibrosis.

Roum, James H., Zea Borok, Noel G.

McElvaney, George J. Grimes, Allan D. Bokser, Roland Buhl and Ronald G.

Crystal. 1Pulmonary Branch, National Heart, Lung, and Blood Institute,

National Institutes of Health, Bethesda, MD 20892, 2Division of Pulmonary

and Critical Care Medicine, University of California Irvine Medical Center,

Orange, CA 92868, 3Pharmacy Department, Warren Grant Magnuson Clinical

Center, National Institutes of Health, Bethesda, MD 20892, 4Department of

Medicine, Division of Pulmonary and Critical Care Medicine, Will Rogers

Institute Pulmonary Research Center, Los Angeles, CA 90033 and 5Division of

Pulmonary Critical Care Medicine, The New York Hospital - Cornell Medical

Center, New York, NY 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 GSH, twice daily, 3 days) to 7 individuals with CF. ELF total,

reduced and oxidized glutathione increased (p<0.05, all comparisons to

pre-GSH therapy) suggesting adequate RES delivery and utilization of GSH.

PMA-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.
 
 

Journal of Applied Physiology 1999 Jul;87(1):438-43