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Acta Anaesthesiol Scand · Apr 2014
Resveratrol attenuates NF-κB-binding activity but not cytokine production in mechanically ventilated mice.
- S E I Van der Wal, M Vaneker, M Kox, G Braak, H W H Van Hees, I A Van den Brink, F M Van de Pol, L M Heunks, J G Van der Hoeven, L A B Joosten, K C P Vissers, and G J Scheffer.
- Department of Anesthesiology, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands.
- Acta Anaesthesiol Scand. 2014 Apr 1;58(4):487-94.
BackgroundMechanical 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.MethodsRVT (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.ResultsMV 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.ConclusionsRVT 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.© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
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