Glasmacinal enhances antiviral responses in bronchial epithelial cells from asthma patients

Background Macrolide antibiotics such as azithromycin (AZM) reduce asthma exacerbations and increase the antiviral defence of bronchial epithelial cells (BECs) from asthma patients. The chronic use of AZM has however raised concerns about antimicrobial resistance. A novel nonantibiotic macrolide, glasmacinal (EP395), is currently being developed as a possible treatment to reduce chronic respiratory disease exacerbations. In this study, we evaluated the effect of glasmacinal on rhinoviral (RV)-induced antiviral and pro-inflammatory genes in BECs from asthma patients. Methods Primary BECs from asthma patients were pre-treated with AZM or glasmacinal for 24 h prior to infection with 0.05 multiplicity of infection RV1B for additional 24 or 48 h. Gene expression of interferon-β (IFN-β), melanoma differentiation-associated gene 5 (MDA5), retinoic acid-inducible gene I (RIG-I), tumour necrosis factor-α (TNF-α), interleukin (IL-6), IL-8, C-C motif chemokine ligand 20 (CCL20) and viral RNA was measured using reverse transcription quantitative PCR. As a marker of cell toxicity, lactate dehydrogenase (LDH) activity was measured in cell supernatants. Results Glasmacinal dose-dependently increased RV-induced mRNA levels of IFN-β (p<0.05), with no additional LDH activity in cell supernatants. RV-induced mRNA expression of MDA5 and RIG-I were also significantly increased with glasmacinal treatment (p<0.05). Concomitantly, viral RNA was significantly reduced by glasmacinal treatment (p<0.01). There was no effect on the RV-induced expression of TNF-α, IL-6, IL-8 or CCL20. These effects were comparable to those of AZM. Conclusions Glasmacinal enhances the antiviral IFN-β, MDA5 and RIG-I response and reduces viral load in BECs from asthma patients. The modulation of epithelial antiviral immunity suggests that glasmacinal may be beneficial in reducing viral-induced asthma exacerbations, although this requires validation in functional and clinical studies.