Resveratrol suppresses persistent airway inflammation and hyperresponsivess might partially via nerve growth factor in respiratory syncytial virus-infected mice

Abstract

Respiratory syncytial virus (RSV) infection is involved in persistent and recurrent wheezing. There are no effective and safe drugs for the sequelae of persistent wheezing after early bronchiolitis. In this study, we investigated the effect of resveratrol on persistent airway inflammation and airway hyperresponsiveness (AHR) induced by RSV infection. RSV-infected mice were sacrificed at serial time points after infection to collect samples and measure the number of inflammatory cells and levels of interferon-gamma (IFN-γ), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF). Airway inflammation, AHR, and the levels of NGF and BDNF were detected after resveratrol administration. Furthermore, Ab-NGF was used to investigate the role of NGF in RSV-induced prolonged airway inflammation and AHR. We found that RSV RNA remained detectable in the lungs of RSV-infected mice on day 60, accompanying persistent airway inflammation and AHR for 60 days. IFN-γ levels in BALF were increased on day 7 but reduced to normal levels by day 14 post-RSV infection, while NGF and BDNF levels gradually increased from day 14 to 60. Furthermore, after resveratrol treatment, the total number of cells in BALF was reduced; the number of inflammatory cells infiltrating the lungs was also lower. Resveratrol attenuated the airway response to methacholine and significantly decreased NGF levels in BALF without affecting BDNF levels. Moreover, airway inflammation and AHR associated with RSV persistence were attenuated after Ab-NGF administration. In all, resveratrol suppresses persistent airway inflammation and AHR might partially through reducing the levels of NGF after RSV infection.