Modeling allergic asthma in mice: Pitfalls and opportunities

Studies in murine experimental models have contributed greatly to understanding the mechanisms of allergic inflammation underlying asthma. However, models involving short-term high-level exposure of sensitized animals to antigen have significant limitations for investigating the pathogenesis of the lesions of chronic asthma. Modeling chronic asthma is problematic, because long-term antigenic challenge often triggers widespread pulmonary parenchymal inflammation or leads to eventual downregulation of inflammation and airway hyperreactivity. We have developed an improved murine model in which animals are exposed to low mass concentrations of aerosolized antigen for 6-8 wk. The mice exhibit airway-specific acute-on-chronic inflammation and changes of airway wall remodeling as seen in human asthma, together with hyperreactivity to a cholinergic agonist which can be specifically attributed to airway disease. This more realistic model of asthma offers a number of opportunities for investigation of pathogenetic mechanisms and novel therapeutic agents.