title: Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells.
abstract: Virus-associated pulmonary exacerbations, often associated with rhinoviruses (RVs), contribute to cystic fibrosis (CF) morbidity. Currently, there are only a few therapeutic options to treat virus-induced CF pulmonary exacerbations. The macrolide antibiotic azithromycin has antiviral properties in human bronchial epithelial cells. We investigated the potential of azithromycin to induce antiviral mechanisms in CF bronchial epithelial cells. Primary bronchial epithelial cells from CF and control children were infected with RV after azithromycin pre-treatment. Viral RNA, interferon (IFN), IFN-stimulated gene and pattern recognition receptor expression were measured by real-time quantitative PCR. Live virus shedding was assessed by assaying the 50% tissue culture infective dose. Pro-inflammatory cytokine and IFN-β production were evaluated by ELISA. Cell death was investigated by flow cytometry. RV replication was increased in CF compared with control cells. Azithromycin reduced RV replication seven-fold in CF cells without inducing cell death. Furthermore, azithromycin increased RV-induced pattern recognition receptor, IFN and IFN-stimulated gene mRNA levels. While stimulating antiviral responses, azithromycin did not prevent virus-induced pro-inflammatory responses. Azithromycin pre-treatment reduces RV replication in CF bronchial epithelial cells, possibly through the amplification of the antiviral response mediated by the IFN pathway. Clinical studies are needed to elucidate the potential of azithromycin in the management and prevention of RV-induced CF pulmonary exacerbations.
authors.affiliation: Division of Paediatric Respiratory Medicine, University Children's Hospital, Berne, Switzerland Dept of Clinical Research, University of Berne, Berne, Switzerland Graduate School for Cellular and Biomedical Sciences, University of Berne, Berne, Switzerland.
authors.forename: Aline
authors.initials: A
authors.lastname: Schögler
authors.affiliation: Division of Paediatric Respiratory Medicine, University Children's Hospital, Berne, Switzerland Dept of Clinical Research, University of Berne, Berne, Switzerland.
authors.forename: Brigitte S
authors.initials: BS
authors.lastname: Kopf
authors.affiliation: Airway Disease Infection Section, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma and Centre for Respiratory Infection, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Edwards
authors.affiliation: Airway Disease Infection Section, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma and Centre for Respiratory Infection, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.affiliation: Division of Paediatric Respiratory Medicine, University Children's Hospital, Berne, Switzerland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Casaulta
authors.affiliation: Division of Paediatric Respiratory Medicine, University Children's Hospital, Berne, Switzerland.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kieninger
authors.affiliation: Division of Respiratory Medicine, University Children's Hospital, Zurich, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.affiliation: Division of Respiratory Medicine, University Children's Hospital, Zurich, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Moeller
authors.affiliation: Dept of Clinical Research, University of Berne, Berne, Switzerland Dept of Pulmonary Medicine, University Hospital Berne, Berne, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Geiser
authors.affiliation: Division of Paediatric Respiratory Medicine, University Children's Hospital, Berne, Switzerland Dept of Clinical Research, University of Berne, Berne, Switzerland These authors contributed equally Nicolas.Regamey@dkf.unibe.ch.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Regamey
authors.affiliation: Division of Paediatric Respiratory Medicine, University Children's Hospital, Berne, Switzerland Dept of Clinical Research, University of Berne, Berne, Switzerland These authors contributed equally.
authors.forename: Marco P
authors.initials: MP
authors.lastname: Alves
mesh_terms: D000293:Adolescent; D000998:Antiviral Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology*; D016022:Case-Control Studies; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000503:physiopathology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006801:Humans; D007223:Infant; D007372:Interferons / Q000378:metabolism; D008297:Male; D010850:Picornaviridae Infections / Q000188:drug therapy; D012229:Rhinovirus
chemical_list: D000998:Antiviral Agents; D017963:Azithromycin; D007372:Interferons