Document Detail


High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis.
MedLine Citation:
PMID:  16537378     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neutrophilic airway inflammation is a hallmark of cystic fibrosis (CF). As high oxidant producers, airway neutrophils contribute largely to the systemic redox imbalance seen in CF. In turn, this chronic and profound imbalance can impact circulating neutrophils before their migration into airways. Indeed, in 18 CF patients with stable disease, blood neutrophils were readily deficient in the pivotal antioxidant glutathione (P = 0.003, compared with 9 healthy controls). In a phase 1 study, this deficiency was improved (P = 0.025) by the glutathione prodrug N-acetylcysteine, given orally in high doses (0.6 to 1.0 g three times daily, for 4 weeks). This treatment was safe and markedly decreased sputum elastase activity (P = 0.006), the strongest predictor of CF pulmonary function. Consistently, neutrophil burden in CF airways was decreased upon treatment (P = 0.003), as was the number of airway neutrophils actively releasing elastase-rich granules (P = 0.005), as measured by flow cytometry. Pulmonary function measures were not improved, as expected with short-term treatment. After excluding data from subjects without baseline airway inflammation, positive treatment effects were more pronounced and included decreased sputum IL-8 levels (P = 0.032). Thus, high-dose oral N-acetylcysteine has the potential to counter the intertwined redox and inflammatory imbalances in CF.
Authors:
Rabindra Tirouvanziam; Carol K Conrad; Teodoro Bottiglieri; Leonore A Herzenberg; Richard B Moss; Leonard A Herzenberg
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Publication Detail:
Type:  Controlled Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-03-13
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  103     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-22     Completed Date:  2006-05-11     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4628-33     Citation Subset:  IM    
Affiliation:
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. tirouvan@stanford.edu
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MeSH Terms
Descriptor/Qualifier:
Acetylcysteine / administration & dosage*
Administration, Oral
Adolescent
Antioxidants / metabolism
Child
Cystic Fibrosis / drug therapy*
Female
Glutathione / analysis,  chemistry,  metabolism*
Humans
Male
Neutrophils / drug effects*
Pancreatic Elastase / metabolism
Pneumonia / drug therapy*
Prodrugs / administration & dosage*
Treatment Outcome
Grant Support
ID/Acronym/Agency:
R01 CA 85949/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Prodrugs; 616-91-1/Acetylcysteine; 70-18-8/Glutathione; EC 3.4.21.36/Pancreatic Elastase
Comments/Corrections

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