Resveratrol attenuates NF-kappaB-binding activity but not cytokine production in mechanically ventilated mice

Contains fulltext : 136061.pdf (publisher's version ) (Closed access)BACKGROUND: Mechanical ventilation (MV) can result in inflammation and subsequent lung injury. Toll-like receptor (TLR)4 and NF-kappaB 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-kappaB. 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-kappaB was measured in lung homogenates. RESULTS: MV resulted in elevated pulmonary concentrations of IL-1beta, IL-6, keratinocyte-derived chemokine (KC) and NF-kappaB DNA-binding activity. RVT at 10, 20 and 40 mg/kg reduced NF-kappaB'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-kappaB activity but does not attenuate cytokine levels. This implies a less prominent role for NF-kappaB in MV-induced inflammation than previously assumed