Epicutaneous Allergen Exposure Dose Determines Manifestation of Allergic Airway Disease in Mice

Rationale:  As cat allergies are associated with severe asthma in children, we sought to determine whether the application of cat dander to barrier-disrupted skin could play a role in the development of allergic asthma. 

Methods:   In 4-6 week old female mice (BALB/c, C57Bl/6 and mice transgenic for the human HLA DRB1*0401), cat dander extract (CDE) was applied (1.5, 15 or 150 μg) to a shaved area on their back for 10 days after tape stripping. Mice were then administered intranasal challenges of CDE to localize the response to the lungs. Eosinophilia was determined by Wright-Giemsa staining of the bronchoalveolar lavage fluid (BALF) and hematoxylin and eosin staining of lung sections. Airway resistance was measured through a nebulized methacholine challenge. 

Results: Mice exposed to 15 μg CDE on the skin showed increased eosinophils in the BALF and peribronchial tissue (BALB/c: 2.3 ± 1.8 x 10⁴ eosinophils and 0.262 ± 0.257 eosinophils/mm² respectively) compared to naive mice (BALB/c: 0.02 ± 0.04 x 10⁴ eosinophils in BALF and 0 eosinophils/mm² in the peribronchial tissue; p <0.05). Airway resistance was also increased. Intriguingly, eosinophilia and airway resistance were markedly reduced in mice that received 150 μg CDE on the skin (BALB/c: 0.5 ± 0.4 x 10⁴ eosinophils in BALF and 0.07 ± 0.05 eosinophils/mm² in the peribronchial tissue). These trends were observed in all three strains.

Conclusions: Although epicutaneous exposure to cat dander on barrier-disrupted skin can lead to allergic airway disease, at a high dose of cat dander on the skin these features of disease are attenuated.