Resveratrol attenuates NF-[kappa]B-binding activity but not cytokine production in mechanically ventilated mice

• Published in: Acta anaesthesiologica Scandinavica Vol. 58; no. 4; p. 487
• Main Authors: Wal, S E I, Vaneker, M, Kox, M, Braak, G, Hees, H W H, Brink, I A, Pol, F M, Heunks, L M, Hoeven, J G, Joosten, L A B, Vissers, K C P, Scheffer, G J
• Format: Journal Article
• Language: English
• Published: Copenhagen Wiley Subscription Services, Inc 01-04-2014
• Subjects: Cytokines; Deoxyribonucleic acid; DNA; Rodents
• ISSN: 0001-5172; 1399-6576
• DOI: 10.1111/aas.12276

Background Mechanical ventilation (MV) can result in inflammation and subsequent lung injury. Toll-like receptor (TLR)4 and NF-[kappa]B 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-[kappa]B. In the present study, we investigated the role of RVT in MV-induced inflammation in mice. Methods RVT (10mg/kg, 20mg/kg and 40mg/kg) or vehicle was intraperitoneally administered 1h before start of MV (4h, tidal volume 8ml/kg, positive end-expiratory pressure 1,5cmH2O and FiO2 0.4). Blood and lungs were harvested for cytokine analysis. DNA binding activity of transcription factor NF-[kappa]B was measured in lung homogenates. Results MV resulted in elevated pulmonary concentrations of IL-1[beta], IL-6, keratinocyte-derived chemokine (KC) and NF-[kappa]B DNA-binding activity. RVT at 10, 20 and 40mg/kg reduced NF-[kappa]B'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-[alpha], KC and IL-6, but RVT did not affect cytokine levels. Conclusions RVT abrogates the MV-induced increase in pulmonary NF-[kappa]B activity but does not attenuate cytokine levels. This implies a less prominent role for NF-[kappa]B in MV-induced inflammation than previously assumed. [PUBLICATION ABSTRACT]