Methods: Female BALB/c mice, 8–10 weeks of age, were used. We developed a mouse model of both acute and chronic asthma in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration. Mice were treated with nintedanib during the OVA challenge.
Results: Compared with control mice, the mice exposed to OVA developed sustained eosinophilic airway inflammation and airway hyperresponsiveness (AHR). Administration of nintedanib significantly decreased total cell and eosinophilic count in bronchoalveolar lavage (BAL) fluid. Also the level of IL-4, 5, and 13 in BAL fluid was significantly lower in nintedanib group compared with control. In a histologic analysis, there were fewer inflammatory cell infiltration in nintedanib group. Nintedanib treatment significantly attenuated airway remodeling including fibrosis and smooth muscle thickening. The protein and gene expression level of VEGF, FGF, and PDGF were lower in nintedanib group. In vitro experiment showed that nintedanib significantly decreased fibroblast proliferation.
Conclusion: These results suggest that nintedanib administration can attenuate airway inflammation, AHR, and remodeling in mouse model of asthma. The beneficial effect of nintedanib was via blocking of VEGF, FGF, and PDGF pathway.