The effect of an oral anti-oxidant, N-Acetyl-cysteine, on inflammatory and oxidative markers in pulmonary sarcoidosis

Respir Med. 2016 Mar;112:106-11. doi: 10.1016/j.rmed.2016.01.011. Epub 2016 Jan 22.

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.

Keywords: N-Acetyl-Cysteine; Oxidative stress; Sarcoidosis.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Acetylcysteine / therapeutic use*
  • Administration, Oral
  • Adult
  • Aged
  • Antioxidants / therapeutic use*
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology*
  • DNA / metabolism*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / metabolism
  • Double-Blind Method
  • Female
  • Glutathione / metabolism*
  • Humans
  • Inflammation
  • Lipopolysaccharides / pharmacology
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Oxidative Stress*
  • Sarcoidosis, Pulmonary / drug therapy*
  • Sarcoidosis, Pulmonary / immunology
  • Sarcoidosis, Pulmonary / metabolism
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Antioxidants
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA
  • Deoxyguanosine
  • Glutathione
  • Acetylcysteine