title: N-acetylcysteine inhibits TNF-alpha, sTNFR, and TGF-beta1 release by alveolar macrophages in idiopathic pulmonary fibrosis in vitro.
abstract: BACKGROUND
  N-acetylcysteine (NAC) can act as an antioxidant. NAC slows the rate of decline of lung function in idiopathic pulmonary fibrosis (IPF) patients concurrently treated with prednisone and azathioprine.
  
  
  OBJECTIVE
  In this study we investigated the effect of NAC on the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12 (p70), IL-18, transforming growth factor (TGF)-beta1, and the soluble TNF receptors (sTNFR1 and sTNFR2) by alveolar macrophages (AM) in IPF patients.
  
  
  METHODS
  AMs were harvested by bronchoalveolar lavage (BAL) from 16 IPF patients and were cultured for 24 h with RPMI medium alone, or with lipopolysaccharide (LPS) (100 ng/ml), in the presence or absence of NAC at various concentrations.
  
  
  RESULTS
  NAC suppressed the production of TNF-alpha, its soluble receptors, and TGF-beta1 by AMs in a dose-dependent manner. At the highest concentration of NAC (10 mM), the spontaneous or LPS-stimulated production ofTNF-alpha, sTNFR1, sTNFR2, and TGF-beta1 were significantly reduced. The LPS-stimulated IL-1beta production was also suppressed by 10 mM NAC.
  
  
  CONCLUSIONS
  NAC has the potential to down-regulate the production of TNF-alpha and their soluble receptors, as well as TGF-beta1 and LPS-stimulated IL-1beta, by AM in IPF in vitro. NAC may have anti-inflammatory and anti-fibrotic effects.
authors.affiliation: Dept of Pneumology and Allergy, Ruhrlandklinik, Medical Faculty, University of Essen, Essen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Cu
authors.forename: Q
authors.initials: Q
authors.lastname: Ye
authors.forename: R
authors.initials: R
authors.lastname: Sarria
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: J
authors.initials: J
authors.lastname: Guzman
authors.forename: U
authors.initials: U
authors.lastname: Costabel
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D016166:Free Radical Scavengers; D018124:Receptors, Tumor Necrosis Factor; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D000111:Acetylcysteine