Effect of Ebastine on Allergen-induced Airway Inflammation and Goblet Cell Metaplasia in Murine Model of Asthma

Histamine H1 receptor antagonists are useful in the treatment of allergic diseases. Recent in vitro experimental studies suggest that H1 receptor antagonists produce their anti-inflammatory effects by inhibition of basal nuclear factor (NF) -κB activity. In the present study, we investigated the effects of ebastine on gene expression, airway inflammation, and goblet cell metaplasia in a murine model of asthma. Groups of mice were sensitized with two intraperitoneal injections of ovalbumin (OVA) on Days 0 and 7. Mice were then challenged intranasally with OVA on Days 24-26 during a course of treatment with either phosphate-buffered saline or ebastine on Days 21-27. After OVA challenge, bronchoalveolar lavage fluid (BALF) and lung tissue specimens were collected. BALF was analyzed for differential cell counts, whereas lung tissue was examined for NF-κB activity and the gene expression of cytokines, chemokines, GATA3, and muc5ac. Lung tissues were stained with periodic acid-Schiff. Airway eosinophilia, increased NF-κB activity, and increased gene expression in the lung of cytokines [interleukin (IL) -4, IL-5, interferon-γ, and tumor necrosis factor-α], chemokines (CCL11, CCL17, and CXCL10), and GATA3 were observed in OVA-sensitized and -challenged mice. These increases were significantly inhibited by ebastine treatment. Moreover, mucus occlusion was significantly inhibited in ebastine-treated mice, with a decrease in muc5ac gene expression compared with untreated mice. These results indicate that ebastine prevents airway inflammation and goblet cell metaplasia in a murine model of asthma partly by inhibiting NF-κB activity and the expression of GATA3.