Establishment of different experimental asthma models in mice.

Asthma is a complex disease. The heterogeneity of airway inflammation during asthma indicates there are different mechanisms involved. In order to further study the mechanisms of asthma, different mouse models were established to mimic corresponding subtypes of asthma in clinic. Eosinophilic asthma was established by intraperitoneal injections of ovalbumin (OVA) on day 0 and day 7, followed by inhalation of aerosolized OVA on days 14-17. Neutrophilic asthma was established by transtracheal administration of a high dose of lipopolysaccharide (LPS; 10 µg) on days 15 and 17 in combination with OVA sensitization and challenge as described previously. Mix-granulocytic asthma was established by transtracheal administration of a low dose of LPS (1 µg) on day 15, in combination with OVA sensitization and challenge as described previously. Compared with healthy controls, increased numbers of eosinophils, elevated levels of T helper (Th)2 cytokines in bronchoalveolar lavage fluid (BALF), and moderated inflammation of lung tissues was observed in eosinophilic asthma. Increased numbers of neutrophils, elevated levels of Th1 and Th17 cytokines in BALF and severe inflammation of lung tissues was observed in neutrophilic asthma. Increased numbers of both eosinophils and neutrophils, elevated levels of Th1, Th2 and Th17 cytokines in BALF and severe inflammation of lung tissues was observed in mix-granulocytic asthma. Airway hyperresponsiveness, increased bronchial mucus secretion, and elevated serum levels of immunoglobin (Ig)E and OVA-IgE were detected in all three asthma models. Dexamethasone reduced the pathogenic symptoms of the mice in eosinophilic asthma, however had no effect on neutrophilic asthma or mix-granulocytic asthma. Each model of asthma established in the present study represents corresponding subtypes of asthma in clinic.