Resveratrol suppresses interferon-gamma-induced biochemical pathways in human peripheral blood mononuclear cells in vitro.
A wide range of biological activities of resveratrol (3,5,4'-trihydroxystilbene) in vitro and in vivo has been proved, including antioxidant, antitumor, and also anti-inflammatory effects. Resveratrol found in, e.g., grapes and red wine has been suggested to counteract the progression of coronary heart disease by lowering serum lipid concentrations and inhibiting platelet aggregation. Cellular immune activation is known to be involved crucially in the pathogenesis of coronary heart diseases. In this in vitro study, the modulatory effect of resveratrol on two interferon-gamma-mediated pathways, the degradation of tryptophan by the enzyme indoleamine 2,3-dioxygenase, and the production of neopterin by activation of the GTP-cyclohydrolase I, was tested. Cultures of human peripheral blood mononuclear cells were exposed to resveratrol, in combination with mitogenic stimulation. A significant down-regulatory effect of resveratrol on both biochemical pathways was found, and also the production of Th1-type cytokine interferon-gamma was significantly suppressed. If these results can be verified in vivo, an explanation is provided how resveratrol may interfere with immune activation and cytokine cascades, which are important in the development and progression of cardiovascular disorders and also other diseases.
Wirleitner
Barbara
B
Division of Biological Chemistry, Biocentre, Innsbruck Medical University, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria.
Schroecksnadel
Katharina
K
Winkler
Christiana
C
Schennach
Harald
H
Fuchs
Dietmar
D
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D003208:Concanavalin A; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000378:metabolism; D015759:Ionomycin; D007476:Ionophores; D007737:Kynurenine / Q000032:analysis; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D019798:Neopterin / Q000096:biosynthesis / Q000378:metabolism; D010835:Phytohemagglutinins; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014364:Tryptophan / Q000032:analysis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007376:Interleukin-2; D007476:Ionophores; D010835:Phytohemagglutinins; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D007737:Kynurenine; D015759:Ionomycin; D019798:Neopterin; D007371:Interferon-gamma; D014364:Tryptophan; D000077185:Resveratrol