RT Journal Article
SR Electronic
T1 Antiviral activity of azithromycin in cystic fibrosis airway epithelial cells
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 3450
VO 44
IS Suppl 58
A1 Aline Schoegler
A1 Brigitte S. Kopf
A1 Ricardo J. Muster
A1 Elisabeth Kieninger
A1 Carmen Casaulta
A1 Andreas Jung
A1 Alexander Moeller
A1 Thomas Geiser
A1 Nicolas Regamey
A1 Marco P. Alves
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/3450.abstract
AB Virus-associated pulmonary exacerbations, most predominantly caused by rhinoviruses (RV), contribute to cystic fibrosis (CF) morbidity. However, there are only few therapeutic options to treat and/or prevent virus-induced CF pulmonary exacerbations. Recent evidence suggests that the macrolide antibiotic azithromycin (AZM) has antiviral properties in RV-infected primary human bronchial epithelial cells. We hypothesize that AZM induces antiviral mechanisms in primary CF bronchial epithelial cells.Primary bronchial epithelial cells from CF children were pretreated with AZM and infected with RV. Viral RNA, interferons (IFNs), IFN-stimulated genes (ISGs), RV pattern recognition receptors (PRRs) expressions were measured by RT-qPCR. Pro-inflammatory cytokine production was assessed by ELISA. Cell death was evaluated by Flow cytometry.After AZM pretreatment, RV load was 7-fold reduced in CF bronchial cells compared to untreated cells (median [interquartile range] 106 copies/reaction: 8.13 [5.28-34.4] vs. 56.8 [18.4-81.5]; p=0.001). The decreased RV load was not due to AZM-induced cytotoxicity in CF bronchial cells. Furthermore, AZM pretreatment significantly increased RV1B-induced IFNs and ISGs, and also PRRs mRNA expression in CF bronchial cells. Interestingly, while stimulating antiviral responses, AZM pretreatment did not significantly prevent virus-induced inflammatory cytokine production.AZM pretreatment reduces RV load in primary paediatric CF bronchial epithelial cells in vitro, possibly by amplifying the antiviral response mediated by the IFNs pathway. This study points to the potential of AZM as a novel therapeutic approach to treat and/or prevent RV-induced CF pulmonary exacerbations.