Topical Application versus Intranasal Instillation: A Qualitative Comparison of the Effect of the Route of Sensitization on Trimellitic Anhydride–Induced Allergic Rhinitis in A/J Mice

Abstract

Allergic airway diseases caused by low-molecular weight chemicals including trimellitic anhydride (TMA) have been linked to Th2 cytokines and are characterized by mucus hypersecretion and infiltration of lymphocytes and eosinophils into the airways. The most common route of human exposure to chemical respiratory allergens is inhalation. Most murine models, however, use topical exposure to sensitize mice. The present study tests the hypothesis that topical sensitization on the ears of mice with TMA will induce a qualitatively similar immunologic and pathologic response in the nasal airways after intranasal challenge to that induced after intranasal sensitization and challenge. A/J mice were sensitized topically or by intranasal instillation followed by intranasal challenge with TMA in an ethyl acetate/olive oil vehicle. Intranasal challenge with TMA in mice that were either topically or intranasally sensitized with TMA caused a marked allergic rhinitis, of similar severity, characterized by an influx of eosinophils and lymphocytes. Both the topical and intranasal routes of sensitization also caused significant increases in total serum IgE after intranasal challenge with TMA. In addition, both the topical and intranasal routes of sensitization caused significant increases in the mRNA expression of the Th2 cytokines IL-4, IL-5, and IL-13. Collectively, these findings suggest that topical application is effective in sensitizing mice to TMA and induces a nasal airway lesion and associated immune response after intranasal challenge, which is qualitatively similar to that induced by intranasal sensitization and challenge. Skin exposure may be a potential route of sensitization of the respiratory tract to chemical allergens.