IL-18 gene transfer by adenovirus prevents the development of and reverses established allergen-induced airway hyperreactivity

We examined the role of IL-18 in preventing the development of and in reversing established allergen-induced airway inflammation and airway hyperreactivity (AHR), the cardinal features of asthma. IL-18, which potently induces IFN-gamma, was administered into the respiratory tract as cDNA in a replication-deficient adenovirus (Adv). Treatment of OVA-sensitized mice with the IL-18-expressing Adv reduced allergen-specific IL-4 production, airway eosinophilia, and mucus production, increased IFN-gamma production, and prevented the development of AHR. The effects of the IL-18 Adv treatment were dependent on the presence of IFN-gamma and IL-12. Moreover, administration of the IL-18 Adv to mice with established AHR greatly reduced AHR and IL-4 production and increased IFN-gamma production. These results demonstrate that IL-18, when administered by Adv into the respiratory tract, effectively reduces AHR and replaces an established Th2-biased immune response with a Th1-biased response.