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.
journal_name
Acta Anaesthesiol Scandjournal_title
Acta anaesthesiologica Scandinavicaauthors
Van der Wal SE,Vaneker M,Kox M,Braak G,Van Hees HW,Van den Brink IA,Van de Pol FM,Heunks LM,Van der Hoeven JG,Joosten LA,Vissers KC,Scheffer GJdoi
10.1111/aas.12276subject
Has Abstractpub_date
2014-04-01 00:00:00pages
487-94issue
4eissn
0001-5172issn
1399-6576journal_volume
58pub_type
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