Anti-IgE efficacy in murine asthma models is dependent on the method of allergen sensitization

Background: Murine models used to delineate mechanisms and key mediators of asthma have yielded conflicting results and suggest that the dominant mech anism and mediators required for disease induction differ depending on the model and method of allergen sensitization used. Objective: The goal of this study was to determine whether the mode of alle rgen sensitization influenced the role that IgE had in allergen-induced pul monary eosinophilic inflammation. Methods: Mice were exposed to dust mite extract in 2 models of allergic inf lammation that differed in the method of sensitization, We compared sensiti zation by aerosol exposure with and without concomitant human respiratory s yncytial virus infection with sensitization by means of systemic (intraperi toneal) exposure with adjuvant, After sensitization, animals were similarly challenged with aerosolized allergen. Animals were treated with anti-IgE m Ab to deplete IgE and to determine its role in the induction of allergic in flammation and mucosa pathology in these models. Results: Concomitant respiratory syncytial virus infection significantly en hanced allergen sensitization by aerosol exposure and exacerbated eosinophi lic inflammation and airway mucosa pathology. Depletion of IgE in this mode l significantly reduced lung eosinophilic inflammation and airway mucose pa thology, However, in the model in which animals were sensitized by means of systemic allergen exposure with adjuvant, depletion of IgE had no ameliora tive effect on lung inflammation or pathology, Conclusion: We demonstrated that the method of antigen sensitization can de lineate the role of IgE in allergen-induced lung inflammation. In a murine model that more closely resembles ambient allergen exposure in human subjec ts, IgE had a critical role in the pathogenesis of allergic asthma and muco sa pathology. The results parallel the results reported with anti-IgE effic acy in allergic asthmatic human subjects.