title: Resveratrol attenuates NF-κB-binding activity but not cytokine production in mechanically ventilated mice.
abstract: BACKGROUND
  Mechanical ventilation (MV) can result in inflammation and subsequent lung injury. Toll-like receptor (TLR)4 and NF-κB are proposed to play a crucial role in the MV-induced inflammatory response. Resveratrol (RVT) exhibits anti-inflammatory effects in vitro and in vivo supposedly by interfering with TLR4 signaling and NF-κB. In the present study, we investigated the role of RVT in MV-induced inflammation in mice.
  
  
  METHODS
  RVT (10 mg/kg, 20 mg/kg and 40 mg/kg) or vehicle was intraperitoneally administered 1 h before start of MV (4 h, tidal volume 8 ml/kg, positive end-expiratory pressure 1,5 cmH2 O and FiO2 0.4). Blood and lungs were harvested for cytokine analysis. DNA binding activity of transcription factor NF-κB was measured in lung homogenates.
  
  
  RESULTS
  MV resulted in elevated pulmonary concentrations of IL-1β, IL-6, keratinocyte-derived chemokine (KC) and NF-κB DNA-binding activity. RVT at 10, 20 and 40 mg/kg reduced NF-κB's DNA-binding activity following MV compared with ventilated controls. However, no differences in cytokine release were found between RVT-treated and control ventilated mice. Similarly, in plasma, MV resulted in elevated concentrations of TNF-α, KC and IL-6, but RVT did not affect cytokine levels.
  
  
  CONCLUSIONS
  RVT abrogates the MV-induced increase in pulmonary NF-κB activity but does not attenuate cytokine levels. This implies a less prominent role for NF-κB in MV-induced inflammation than previously assumed.
authors.affiliation: Department of Anesthesiology, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands.
authors.forename: S E I
authors.initials: SE
authors.lastname: Van der Wal
authors.forename: M
authors.initials: M
authors.lastname: Vaneker
authors.forename: M
authors.initials: M
authors.lastname: Kox
authors.forename: G
authors.initials: G
authors.lastname: Braak
authors.forename: H W H
authors.initials: HW
authors.lastname: Van Hees
authors.forename: I A
authors.initials: IA
authors.lastname: Van den Brink
authors.forename: F M
authors.initials: FM
authors.lastname: Van de Pol
authors.forename: L M
authors.initials: LM
authors.lastname: Heunks
authors.forename: J G
authors.initials: JG
authors.lastname: Van der Hoeven
authors.forename: L A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: K C P
authors.initials: KC
authors.lastname: Vissers
authors.forename: G J
authors.initials: GJ
authors.lastname: Scheffer
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D004247:DNA / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006321:Heart / Q000187:drug effects / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism*; D012121:Respiration, Artificial; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D016328:NF-kappa B; D013267:Stilbenes; D004247:DNA; D000077185:Resveratrol