Intranasal dupilumab improves responsiveness to steroid in an asthma mouse model

Aims: The study aimed to evaluate the efficacy of local intranasal delivery of dupilumab, a monoclonal antibody targeting IL-4Rα, in comparison to intraperitoneal delivery in a mouse model of steroid-hyporesponsive asthma, a condition characterized by limited therapeutic options. Methods: Dupilumab was administered via both intranasal and intraperitoneal routes to a mouse model of steroid-hyporesponsive asthma. The efficacy of the treatment was assessed through histological evaluations of inflammation and goblet cell metaplasia, analysis of immune cell infiltration in bronchoalveolar lavage fluid via cytospin, and measurement of total airway resistance using FlexiVent. Additionally, gene and protein expression related to steroid hypo-responsiveness and tissue remodeling were analyzed. Results: Intranasal administration of dupilumab significantly reduced inflammation and goblet cell metaplasia in the bronchial epithelium. It also led to a decrease in immune cell infiltration in bronchoalveolar lavage fluid and reduced total airway resistance. Furthermore, the intranasal dupilumab-treated group exhibited lower expression of genes and proteins associated with steroid hypo-responsiveness and tissue remodeling. Conclusions: Our findings demonstrate that intranasal administration of dupilumab not only effectively reduces inflammation but also significantly reverses steroid hypo-responsiveness and tissue remodeling, outperforming systemic delivery. Thus, local intranasal administration of dupilumab offers superior therapeutic benefits in managing steroid-hyporesponsive asthma.