title: Resveratrol decreases oxidative burst capacity and alters stimulated leukocyte cytokine production in vitro.
abstract: BACKGROUND
  Resveratrol, a naturally-occurring phytophenol, has been shown to bolster immune surveillance and reverse immunosenescence in a dose dependent manner in rodents and humans. Although safety and pharmacokinetic studies have been completed in dogs, the immunomodulatory effects of resveratrol in dogs has not yet been investigated. The objective of this study was to determine the effect of resveratrol on canine innate immune system function in vitro. The hypothesis was that similar to other species, low concentrations of resveratrol would stimulate while high concentrations would depress innate immune system function.
  
  
  METHODS
  Whole blood was collected from six healthy, adult, client-owned dogs and was incubated with resveratrol at final concentrations of 6000 ng ml(-1), 3000 ng ml(-1), 1000 ng ml(-1), or control solution for 4h. Following incubation, phagocytosis and oxidative burst were evaluated using flow cytometry, and LPS-, lipoteichoic acid (LTA) - and peptidoglycan (PG)-stimulated leukocyte production of TNF, IL-6, and IL-10 were measured using a canine specific multiplex assay.
  
  
  RESULTS
  Phagocytosis was not altered by resveratrol at any concentration compared to control. However, while the number of PMNs capable of performing oxidative burst did not change, the robustness of the reaction following stimulation with Escherichia coli and PMA was reduced in a dose dependent manner. In addition, LPS-, LTA-, PG, and PBS-stimulated TNF production was increased following incubation with all concentrations of resveratrol compared to control, and this effect was dose dependent. LTA-stimulated IL-6 was increased with resveratrol compared to control. Furthermore, LTA-stimulated IL-10 was decreased with 6000 ng ml(-1) and 3000 ng ml(-1) concentrations of resveratrol and PG-stimulated IL-10 production was decreased with all concentrations of resveratrol compared to control. The LPS-, LTA-, and PG-stimulated TNF:IL-10 ratio was increased with 6000 ng ml(-1) of resveratrol compared to control and lower resveratrol concentrations.
  
  
  CONCLUSIONS
  While resveratrol was sparing to PMN phagocytosis, it reduced the robustness of PMN oxidative burst. Resveratrol also increased pro-inflammatory and decreased anti-inflammatory leukocyte cytokine production capacity in vitro. These data suggest that resveratrol supplementation may depress oxidative burst reactions while promoting pro-inflammatory leukocyte cytokine production and decreasing anti-inflammatory cytokine production. Based on these findings, further in vivo study regarding the effects of resveratrol on PMN oxidative burst capability and leukocyte cytokine production capacity are indicated prior to routine supplementation.
authors.affiliation: Comparative Oncology Laboratory, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, MO 65211, USA; Comparative Internal Medicine Laboratory, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, MO 65211, USA.
authors.forename: Rowena A
authors.initials: RA
authors.lastname: Woode
authors.affiliation: Comparative Oncology Laboratory, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, MO 65211, USA. Electronic address: bechtels@missouri.edu.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Axiak-Bechtel
authors.affiliation: Comparative Internal Medicine Laboratory, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, MO 65211, USA.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tsuruta
authors.affiliation: Comparative Internal Medicine Laboratory, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, MO 65211, USA.
authors.forename: Juliana R
authors.initials: JR
authors.lastname: Amorim
authors.affiliation: Comparative Internal Medicine Laboratory, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, MO 65211, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Comparative Internal Medicine Laboratory, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, MO 65211, USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: DeClue
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004285:Dogs / Q000097:blood*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis; D016897:Respiratory Burst / Q000187:drug effects*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D013267:Stilbenes; D000077185:Resveratrol
keywords: Innate immunity; Macrophages; Neutrophils; Phagocytosis; Phytophenol; Pro-inflammatory cytokines