title: Resveratrol intake enhances indoleamine-2,3-dioxygenase activity in humans.
abstract: BACKGROUND
  Resveratrol is a polyphenol compound found in various nutrients that was shown to have immunomodulatory, anti-cancerogenic, and cardioprotective effects. The regulation of indoleamine-2,3-dioxygenase (IDO), the rate-limiting enzyme in inflammatory tryptophan metabolism, has been proposed to be involved in resveratrol's biological effects. These observations, however, rely on in vitro findings and animal studies. Therefore, we assessed the impact of resveratrol on tryptophan metabolism after oral intake in humans.
  
  
  METHODS
  Healthy volunteers were orally administrated 5g resveratrol (n=8) or placebo (n=2) in a pilot study. IDO activity was determined by analyzing plasma levels of tryptophan and kynurenine. Determination of the immune activation marker neopterin was included in the analysis.
  
  
  RESULTS
  Resveratrol administration significantly reduced tryptophan levels 2.5h (p<0.001) and 5h (p<0.001) after treatment. Kynurenine levels were slightly, but not significantly, elevated 2.5h after the intervention, which resulted in an 1.33- and 1.30-fold increase of the kynurenine to tryptophan ratio at 2.5h (p<0.01) and 5h (p<0.01), respectively. Neopterin levels were not affected by resveratrol administration.
  
  
  CONCLUSIONS
  This is the first evidence of a modulatory effect of orally administered resveratrol on tryptophan metabolism in humans. Since IDO has been shown to play a crucial role in immunity, cancer development and regulation of vascular tone, the modulation of this enzyme might be involved in resveratrol's diverse biological effects.
authors.affiliation: Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria. Electronic address: guido.gualdoni@meduniwien.ac.at.
authors.forename: Guido A
authors.initials: GA
authors.lastname: Gualdoni
authors.affiliation: Division of Biological Chemistry, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.affiliation: Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria.
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Zlabinger
authors.affiliation: Division of Medical Biochemistry, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Gostner
mesh_terms: D000284:Administration, Oral; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007737:Kynurenine / Q000378:metabolism; D008297:Male; D019798:Neopterin / Q000378:metabolism; D010865:Pilot Projects; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D014364:Tryptophan / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D013267:Stilbenes; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan; D000077185:Resveratrol
keywords: IDO; Immunomodulation; Kynurenine; Resveratrol; Tryptophan