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

• Published in: Acta anaesthesiologica Scandinavica Vol. 58; no. 4; pp. 487 - 494
• Main Authors: VAN DER WAL, S. E. I., VANEKER, M., KOX, M., BRAAK, G., VAN HEES, H. W. H., VAN DEN BRINK, I. A., VAN DE POL, F. M., HEUNKS, L. M., VAN DER HOEVEN, J. G., JOOSTEN, L. A. B., VISSERS, K. C. P., SCHEFFER, G. J.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-04-2014
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Cytokines - analysis; Cytokines - biosynthesis; DNA - metabolism; Enzyme-Linked Immunosorbent Assay; Heart - drug effects; Heart - physiology; Lung - drug effects; Lung - physiology; Male; Mice; Mice, Inbred C57BL; NF-kappa B - drug effects; NF-kappa B - metabolism; Respiration, Artificial; Stilbenes - pharmacology
• 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‐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 cmH2O 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.