The epidermal growth factor receptor inhibitor AG1478 inhibits eosinophilic inflammation in upper airways

Mucus hypersecretion and eosinophil infiltration are important characteristics of eosinophilic inflammation in upper airways, such as allergic rhinitis and chronic rhinosinusitis with nasal polyp. EGFR transactivation induces mucus and inflammatory cytokine secretion from airway epithelial cells. However, the roles of EGFR in eosinophilic inflammation in upper airways are still unknown. The purpose of the study is to elucidate the effects of the EGFR inhibitor AG1478 on eosinophilic airway inflammation. AG1478 significantly inhibited thrombin-induced GM-CSF secretion from nasal epithelial cells and thrombin-induced secretion of eotaxin-1 and RANTES from nasal fibroblasts. Intranasal instillation of AG1478 inhibited OVA-induced goblet cell metaplasia, mucus production and eosinophil/neutrophil infiltration in rat nasal epithelium, as did intraperitoneal injection of AG1478. These results indicate that EGFR transactivation plays an important role in eosinophilic airway inflammation. Intranasal instillation of an EGFR inhibitor may be a new therapeutic approach for the treatment of intractable eosinophilic inflammation in upper airways.