Azithromycin induces anti-viral responses in bronchial epithelial cells

Eur Respir J. 2010 Sep;36(3):646-54. doi: 10.1183/09031936.00095809. Epub 2010 Feb 11.


The majority of asthma exacerbations are caused by rhinovirus. Currently the treatment of asthma exacerbations is inadequate. Previous evidence suggests that macrolide antibiotics have anti-inflammatory and antiviral effects; however, the mechanism is unknown. We investigated the anti-rhinoviral potential of macrolides through the induction of antiviral gene mRNA and protein. Primary human bronchial epithelial cells were pre-treated with the macrolides azithromycin, erythromycin and telithromycin, and infected with minor-group rhinovirus 1B and major-group rhinovirus 16. The mRNA expression of the antiviral genes, type I interferon-β and type III interferon-λ1, interferon-λ2/3, and interferon-stimulated genes (retinoic acid inducible gene I, melanoma differentiation associated gene 5, oligoadenylate synthase, MxA and viperin) and pro-inflammatory cytokines (interleukin (IL)-6 and IL-8), and rhinovirus replication and release were measured. Azithromycin, but not erythromycin or telithromycin, significantly increased rhinovirus 1B- and rhinovirus 16-induced interferons and interferon-stimulated gene mRNA expression and protein production. Furthermore, azithromycin significantly reduced rhinovirus replication and release. Rhinovirus induced IL-6 and IL-8 protein and mRNA expression were not significantly reduced by azithromycin pre-treatment. In conclusion, the results demonstrate that azithromycin has anti-rhinoviral activity in bronchial epithelial cells and, during rhinovirus infection, increases the production of interferon-stimulated genes.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Antiviral Agents / pharmacology*
  • Azithromycin / pharmacology*
  • Bronchi / drug effects
  • Bronchi / virology*
  • Cytokines / metabolism
  • DNA Primers / genetics
  • DNA, Complementary / metabolism
  • Enzyme-Linked Immunosorbent Assay / methods
  • Epithelial Cells / virology*
  • Humans
  • Inflammation
  • Interferons / metabolism
  • Lung / virology
  • Picornaviridae Infections / metabolism
  • RNA, Messenger / metabolism


  • Anti-Bacterial Agents
  • Antiviral Agents
  • Cytokines
  • DNA Primers
  • DNA, Complementary
  • RNA, Messenger
  • Azithromycin
  • Interferons