Effects of Dexamethasone on Tissue Injury and Reconstruction in Ethanol/Steroid Injection Therapy for Allergic Rhinitis

Background: Conventional therapies involving radiofrequency tissue ablation or laser cauterization for allergic rhinitis are accompanied by lesioning and restoration of the mucosa, which are important healing processes for this therapy but difficult to control in their extent. To overcome this problem, we developed a therapeutic method based on the injection of ethanol (E) containing a glucocorticoid into the nasal mucosa; however, the mechanistic aspects of this method remain to be investigated. Objective: We first developed a mouse model of the tissue injury for therapeutic processes of allergic rhinitis by using skin tissues and then clarified the effectiveness of the glucocorticoid in the healing process of the tissue lesion caused by ethanol using the model. Methods: We injected 70% (v/v) E containing 0.1% dexamethasone (E/Dex), 70% (v/v) E, or saline (Sa) into the dermis of mouse skin. Histological analysis of tissue damage, quantitative analyses of inflammatory cytokine and chemokine expressions, and histological and quantitative analyses of some extracellular matrix molecules were performed. Results: Histological comparisons of damaged tissues performed using the skin model qualified it as an effective mimic of the nasal mucosa. In the model, the inclusion of Dex in the injection of E/Dex dramatically ameliorated tissue damage by significantly attenuating expressions of neutrophil chemotactic chemokines, such as keratinocyte chemokine and macrophage inflammatory protein-2, and pro-inflammatory cytokines, such as interleukin-1β, interleukin-6, and osteopontin, compared to the injection of E alone. Inflammatory cell recruitment was also suppressed after the injection of E/Dex. Hyaluronan and versican expression increased after E injection, but hyaluronan expression was markedly suppressed after E/Dex injection. Conclusion: We confirmed that Dex alleviates the tissue damage caused by ethanol-induced activated neutrophils via suppression of neutrophil chemotactic chemokines and pro-inflammatory cytokines and reduction of the inflammatory extracellular matrix, which reveals the effectiveness of glucocorticoids in our developing injection therapy.