The Effect of the Novel Macrolide Glasmacinal (EP395) on Allergen-Induced Eosinophil Infiltration into the Lung.

PURPOSE: Patients with frequent exacerbations of COPD despite bronchodilator therapy may benefit from inhaled corticosteroids (ICS) if they have eosinophilic inflammation. For those who exacerbate despite bronchodilators plus ICS treatment, or who are not candidates for ICS, use of azithromycin (AZM) off-label may be considered as an add on therapy. Glasmacinal (EP395) is a non-antibiotic macrolide that enhances airway epithelial function and immune defence properties and reduces neutrophilic inflammation in preclinical models. Here, we present the effects of glasmacinal on eosinophilic inflammation in preclinical models of allergic inflammation. METHODS: Glasmacinal was tested in two established models of eosinophil-infiltration airway inflammation: an ovalbumin (OVA)-induced mouse model and a house-dust mite (HDM)-induced guinea pig model. Following sensitisation, animals were pretreated with glasmacinal for 2 weeks prior to challenge. In the OVA model, budesonide- and in the HDM model, AZM- treated animals were also included as comparators. Endpoints included differential cell counts, Th1 and Th2 cytokines in bronchoalveolar lavage fluid (BALF) and/or plasma, and lung histology and vascular permeability. RESULTS: Glasmacinal significantly reduced allergen challenge-induced eosinophilia in both models. In the OVA model, glasmacinal dose-dependently (0.4, 1, 2 mg/kg) decreased Th1 and Th2 cytokines, with significant reductions at 1 and 2 mg/kg. In the HDM model, glasmacinal preserved lung morphology, reduced mucus accumulation and collagen deposition, and significantly lowered plasma IL-4 and BALF IL-6 levels. CONCLUSION: Glasmacinal attenuated eosinophilic airway inflammation in two preclinical models, supporting its potential as a novel therapy for reducing exacerbations in COPD and asthma.