title: The effect of an oral anti-oxidant, N-Acetyl-cysteine, on inflammatory and oxidative markers in pulmonary sarcoidosis.
abstract: BACKGROUND
  Oxidative stress (OS) has been shown to play a role in the pathogenesis of sarcoidosis and previous studies have shown that anti-oxidants can reduce markers of oxidative stress and inflammation in the peripheral blood of sarcoidosis subjects. We investigated the effect of N-Acetyl-Cysteine (NAC) on oxidative stress and inflammatory markers in the lungs of sarcoidosis patients.
  
  
  METHODS
  We randomized 11 sarcoidosis subjects to active therapy and 3 to placebo for 8 weeks in a double blinded study. Bronchoscopy with bronchoalveolar lavage was performed pre and post therapy. Our primary endpoint was TNF-α production from stimulated and unstimulated BAL cells. Secondary outcomes included measures of oxidative stress (GSH, 8-OHdG) levels in the BAL. In-vitro studies were also performed to assess the effect of NAC on lipopolysaccharide stimulated BAL cell production of TNF-α.
  
  
  RESULTS
  Eight subjects in the active group and 2 in the placebo group completed the study protocol. Eight weeks of oral NAC did not have a significant impact on TNF-α levels from BAL cells in-vivo in spite of a 59% increase in BAL GSH levels. Our in vitro studies showed a significant decline in TNF-α production from LPS stimulated BAL cells treated with 5 and 10 mM of NAC.
  
  
  CONCLUSIONS
  Oral NAC increased GSH levels but failed to suppress in-vivo TNF-α production in contrast to effects in-vitro. Anti-oxidant therapy may still play a role in the management of sarcoidosis but therapy with better bioavailability or potency is needed to suppress the lung inflammatory response.
authors.affiliation: Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, United States. Electronic address: hamzehn@njhealth.org.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Hamzeh
authors.affiliation: Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, United States.
authors.forename: Briana
authors.initials: B
authors.lastname: Barkes
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, United States.
authors.forename: Beth
authors.initials: B
authors.lastname: Canono
authors.affiliation: Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, United States.
authors.forename: May
authors.initials: M
authors.lastname: Gillespie
authors.affiliation: Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Maier
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Day
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000111:Acetylcysteine / Q000627:therapeutic use*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D004247:DNA / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017565:Sarcoidosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology*
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; D005978:Glutathione; D000111:Acetylcysteine
keywords: N-Acetyl-Cysteine; Oxidative stress; Sarcoidosis