Abstract
Background: Rhinovirus infection is a major cause of difficult-to-treat asthma exacerbations. Azithromycin, a macrolide antibiotic, induces epithelial interferon expression in vitro (Gielen, V. et al. Eur Respir J 2010; 36:646-54) and has been shown to decrease exacerbation frequency in a non-eosinophilic subset of asthma patients (Brusselle, G.G. et al. Thorax 2013; 68:322-9). However, its mode of action is still not fully elucidated.
Aim: Our study aimed to assess antiviral interferon responses to azithromycin treatment in an experimental mouse model of asthma exacerbation.
Methods: C57BL/6 mice were challenged with house dust mite (HDM) for 3 weeks, which has previously been shown to be a mixed neutrophilic-eosinophilic model, and were subsequently exposed to 3 doses of poly(I:C). Mice were treated with azithromycin 48h before and during poly(I:C) stimulation once a day. The experiment was terminated 24h after the final poly(I:C) exposure. Bronchial alveolar lavage fluid (BALF) and lungs were collected.
Results: Azithromycin increased the expression of type I (IFNβ, p < 0.05) and type III (IFNλ1, p < 0.05) interferons in lungs compared to vehicle control. This was accompanied by an over-expression of TLR3 (p < 0.05) but not RIG-I. Gene expression of IRF3 and IRF7 followed the same pattern as interferon expression. There was no change in the number of total BALF cells by azithromycin treatment.
Conclusion: This study demonstrates azithromycin-induced lung expression of type I and III interferons in a mouse asthma exacerbation model in vivo. We suggest that azithromycin-induced antiviral interferons may be therapeutically beneficial in viral-induced exacerbations of asthma.
- Copyright ©ERS 2015