New Model of Murine Allergic Rhinosinusitis Induced Cockroach Allergens

Rationale: Allergic rhinosinusitis is a common comorbidity in patients with allergic asthma. There is believed to be a pathophysiologic overlap between asthma and allergic rhinitis similar histopathologic inflammation and remodeling. Up to this point previous models required chronic daily exposure to clinically irrelevant allergens to induce histopathologic change. This study examined murine nasal epithelial changes following allergic rhinitis induction with a clinically relevant allergen.  

Methods: Six week old female ICR mice were sensitized according to our asthma protocol via intratracheal instillation of (2)25 μL aliquots of 1:10 dilution cockroach allergen (CRA) Blag1 and Blag2 versus vehicle on day 0 and 14, with third allergen challenge on day 21.  At the indicated timepoints after final challenge, plasma, nasal lavage, and sinus histology were collected for analysis.

Results:  Morphometric analysis of nasal cavity measurement showed no significant difference in airway patency. Nasal lavage of CRA-exposed mice showed a significant increase in eosinophils and neutrophils relative to vehicle mice (3.83x10⁶cells/mL versus 4.20x10⁴cells/mL p=0.0344). There was a significant increase in lamina propria thickness underlying olfactory epithelium at the superior nasal vault (51.2±2.4μm versus 65.61±2.2μm p<0.0001), with relative Bowman gland hypertrophy compared to control mice.  Respiratory epithelium and submucosal glands had a 2-fold increase in mucin compared to controls (MGV 4.67±0.7 versus 1.62±0.15, p=0.0112).

Conclusions: This is a clinically relevant model in which allergic rhinitis was induced in mice without direct interference with nasal passages. The model shows significant pathologic changes (increased eosinophils, neutrophils, lamina propria thickening) that reproduce findings observed in patients.