PT  - JOURNAL ARTICLE
AU  - Aline Schoegler
AU  - Brigitte S. Kopf
AU  - Ricardo J. Muster
AU  - Elisabeth Kieninger
AU  - Carmen Casaulta
AU  - Andreas Jung
AU  - Alexander Moeller
AU  - Thomas Geiser
AU  - Nicolas Regamey
AU  - Marco P. Alves
TI  - Antiviral activity of azithromycin in cystic fibrosis airway epithelial cells
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - 3450
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/3450.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/3450.full
SO  - Eur Respir J2014 Sep 01; 44
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.