title: Resveratrol enhances TNF-α production in human monocytes upon bacterial stimulation.
abstract: BACKGROUND
  Resveratrol is a key component of red wine that has been reported to have anti-carcinogenic and anti-aging properties. Additional studies conducted in vitro and in animal models suggested anti-inflammatory properties. However, data from primary human immune cells and in vivo studies are limited.
  
  
  METHODS
  A pilot study was performed including 10 healthy volunteers. Plasma cytokine levels were measured over 48h after oral application of 5g resveratrol. To verify the in vivo findings, cytokine release and gene expression in human peripheral blood mononuclear cells (PBMC) and/or monocytes was assessed after treatment with resveratrol or its metabolites and stimulation with several toll-like receptor (TLR)-agonists. Additionally, the impact on intracellular signaling pathways was analyzed using a reporter cell line and Western blotting.
  
  
  RESULTS
  Resveratrol treated individuals showed a significant increase in tumor necrosis factor-α (TNF-α) levels 24h after treatment compared to baseline. Studies using human PBMC or isolated monocytes confirmed potentiation of TNF-α production with different TLR agonists, while interleukin (IL)-10 was inhibited. Moreover, we observed significantly enhanced nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) activation using a reporter cell line and found increased phosphorylation of p105, which is indicative of alternative NF-κB pathway activation.
  
  
  CONCLUSIONS
  By administering resveratrol to healthy humans and utilizing primary immune cells we were able to detect TNF-α enhancing properties of the agent. In parallel, we found enhanced alternative NF-κB activation. We report on a novel pro-inflammatory property of resveratrol which has to be considered in concepts of its biologic activity.
authors.affiliation: Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria. Electronic address: guido.gualdoni@meduniwien.ac.at.
authors.forename: Guido A
authors.initials: GA
authors.lastname: Gualdoni
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Kovarik
authors.forename: Johannes
authors.initials: J
authors.lastname: Hofer
authors.forename: Franziska
authors.initials: F
authors.lastname: Dose
authors.forename: Marc
authors.initials: M
authors.lastname: Pignitter
authors.forename: Daniel
authors.initials: D
authors.lastname: Doberer
authors.forename: Peter
authors.initials: P
authors.lastname: Steinberger
authors.forename: Veronika
authors.initials: V
authors.lastname: Somoza
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Zlabinger
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010865:Pilot Projects; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000008:administration & dosage* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D000077185:Resveratrol
keywords: FLA; GAPDH; IL; Immunomodulation; LPS; MAPK; Monocyte; NF-κB; PBMC; PBS; Resveratrol; SAC; Signaling; Staphylococcus aureus cells; TNF-α; Toll-like receptor; Tumor necrosis factor-α; flagellin; glyceraldehyde 3 phosphate dehydrogenase; interleukin; lipolysaccharide; mitogen activated protein kinase; nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells; peripheral blood mononuclear cells; phosphate buffered saline; tumor necrosis factor-α