Developing a chronic murine model that better reflects the clinical features of the human asthma

Background: Murine models are useful for the investigation of pathogenesis of asthma. However, chronic antigen exposures in mice lead to immune tolerance, resulting in waning of the airway inflammation and hyper-responsiveness (AHR). The generation of optimized chronic murine models of asthma is crucial to recapitulate the principal characteristics of the features of human asthma. Objective: The aim of this study was to develop chronic murine asthma models that mostly simulate human asthma. Methods: BALB/c and C57BL/c mice were sensitized with intra-peritoneal administration of either ovalbumin (OVA) 20 mcg or house dust mite (HDM) allergen 100 mcg emulsified with aluminum hydroxide on day 0 and 14. Phosphate buffered saline, commercial OVA or various doses (0∼300 mcg) of HDM allergens were given intra-nasally two times a week for 12 weeks from day 21. AHR was measured at 24hr after the last allergen exposure. Broncho-alveolar lavage (BAL) fluid and lung tissues were collected 48hr after the last allergen exposure. Goblet cell hyperplasia and sub-epithelial fibrosis were compared between various groups. Results: BALB/c mice showed more increment in AHR, but airway inflammations were similar in BALB/c and C57BL/c strains. HDM allergeninduced more and longer airway inflammation (optimal dose was 100 mcg) than OVA. But, AHR, goblet cell hyperplasia, and sub-epithelial fibrosis were similar with OVA. Conclusion: HDM allergen challenge (100 mcg) to BALB/c mice for 12 weeks was effective to generate chronic murine asthma model.