084 Inhaled Doxycycline reduces allergen-induced airway inflammation, hyperresponsiveness and remodelling in mice

Introduction Asthma is an inflammatory disease of the airways leading to branchial morphological changes. Matrix metalloprotei-nases (MMPs) are thought to be responsible for a significant part of the allergen-driven inflammation and airway remodelling. The aim of the present study was to assess the effect of doxycycline, a potent MMP inhibitor, given by inhalation on airway inflammation, res-ponsiveness and remodelling. Methods BALB/c mice were sensitized at day 1 and 8 and exposed to aerosolized ovalbumin (OVA) from day 21 to 27 (short term exposure STE) or 5 days/odd weeks from day 22 to 96 (long term exposure LTE). Mice were exposed 30’ before each allergen inhalation to placebo (PBS), excipient alone, doxycycline, or fluti-casone. ResultS In STE model, doxycycline and fluticasone (used as a reference therapy) decreased the allergen-induced eosinophilic inflammation, methacholine-induced airway responsiveness, and peribronchial inflammation. In the LTE model, doxycycline and fluticasone decreased significantly the glandular hyperplasia, the airway wall thickness, and the collagen deposition in the bronchi which are major features of airway remodelling. Doxycycline inhalation did induce a huge increase in IL-10 levels and a decrease in IL-5 and IL-13 levels and decreased the proportion of activated MMP-9 measured in the lung extracts. Conclusion Inhaled doxycycline decreases the allergen-induced airway inflammation and responsiveness and prevents the occurrence of a branchial remodelling in a mouse model of asthma.