title: Antioxidant status associated with inflammation in sarcoidosis: a potential role for antioxidants.
abstract: BACKGROUND
  Enhanced production of reactive oxygen species (ROS), capable of reducing endogenous defense levels and enhancing inflammation, is suggested to play a role in sarcoidosis. Antioxidant supplementation might offer protection against such ROS-mediated damage. A promising candidate for antioxidant supplementation is the flavonoid quercetin.
  
  
  OBJECTIVE
  To determine the antioxidant and inflammatory status in sarcoidosis. Furthermore, the potential of quercetin to mitigate the occurring inflammation will be assessed.
  
  
  METHODS
  Non-smoking sarcoidosis patients and healthy controls matched for age, gender and dietary behavior were enrolled (NCT-00512967). Measurements included assessment of total plasma antioxidant capacity, vitamin C, uric acid, glutathione, basal and LPS-induced levels of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-8 and -10 as well as the effect of quercetin on these levels.
  
  
  RESULTS
  Compared to their controls, the sarcoidosis patients displayed significantly lower total plasma antioxidant capacity, decreased levels of vitamin C, uric acid and glutathione and increased levels of basal TNFalpha and IL-8. Quercetin significantly decreased ex vivo LPS-induced TNFalpha- and IL-8 production in a concentration-dependent manner in both groups. Interestingly, this quercetin effect was more pronounced in sarcoidosis patients.
  
  
  CONCLUSIONS
  The endogenous antioxidant defense was significantly reduced in sarcoidosis, indicating that oxidative stress underlies the pathology of this disease. Furthermore, the inflammatory status was significantly enhanced in sarcoidosis. Finally, our results regarding the effect of quercetin on cytokine production imply that sarcoidosis patients might benefit from antioxidant supplementation not only by empowering the relatively low protection against ROS but also by reducing inflammation.
authors.affiliation: Department of Pharmacology and Toxicology, Maastricht University, The Netherlands. a.boots@farmaco.unimaas.nl
authors.forename: Agnes W
authors.initials: AW
authors.lastname: Boots
authors.forename: Marjolein
authors.initials: M
authors.lastname: Drent
authors.forename: Els L R
authors.initials: EL
authors.lastname: Swennen
authors.forename: Harald J J
authors.initials: HJ
authors.lastname: Moonen
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
authors.forename: Guido R M M
authors.initials: GR
authors.lastname: Haenen
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000032:analysis* / Q000494:pharmacology; D001205:Ascorbic Acid / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002839:Chromans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005978:Glutathione / Q000097:blood; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011794:Quercetin / Q000494:pharmacology; D012507:Sarcoidosis / Q000097:blood* / Q000276:immunology / Q000503:physiopathology; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014527:Uric Acid / Q000097:blood
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002839:Chromans; D005419:Flavonoids; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014527:Uric Acid; D011794:Quercetin; D005978:Glutathione; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid