Azithromycin induces anti-viral responses in bronchial epithelial cells.
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.
Dept of Respiratory Medicine National Heart & Lung Institute St Mary's Campus, Imperial College London, MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, W2 1PG, London, UK.
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V
Gielen
S L
SL
Johnston
M R
MR
Edwards
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects / Q000821:virology*; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004847:Epithelial Cells / Q000821:virology*; D006801:Humans; D007249:Inflammation; D007372:Interferons / Q000378:metabolism; D008168:Lung / Q000821:virology; D010850:Picornaviridae Infections / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D016207:Cytokines; D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D017963:Azithromycin; D007372:Interferons