BALB/c mice are sensitized with an intranasal (IN) administration of HDM on days 0 and 7. Mice are then challenged with HDM intranasally on Day 14 and endpoints are assessed on day 15. Reference treatment animals receive 3 mg/kg dexamethasone 1 hour prior to the challenge.

Total cells, eosinophils, and neutrophils recovered in broncho-alveolar lavage fluid on day 15 of an HDM-induced acute allergic asthma model. Sensitized and challenged mice demonstrate an increase in total cells, eosinophils, and neutrophils. 3 mg/kg dexamethasone treatment lowered total cells, eosinophils, and neutrophils in the BAL fluid.

Lung Resistance is measured on day 15 of an HDM-induced acute allergic asthma model, following exposure to increasing doses of methacholine. Animals that are sensitized and challenged with HDM display increased lung resistance in comparison to Naïve animals. 3 mg/kg Dexamethasone or 1 mg/kg Fluticasone Propionate (FP) treatments reduced airway hyperreactivity in diseased animals.

H&E- and PAS-stained lung sections from naïve mice and mice from an HDM-induced acute allergic asthma model on day 15. Infiltration of mixed inflammatory cells are observed in diseased animals in comparison to Naïve animals. Increases in multifocal inflammation within alveolar spaces (black arrow) and surrounding vessels (red arrows) are observed in lungs of diseased animals. Larger bronchioles lined with moderate numbers of PAS-positive goblet cells (green arrows) can be seen in lungs of diseased animals whereas saline control lungs had PAS-negative cells (black arrows).

Significant increases in Th2 inflammatory mediators (IL-4, IL-5, and IL-6) are observed in BAL fluid of diseased animals, though changes in IL-1β, a Th1 cytokine are not observed. Levels of IL-4, IL-5, and IL-6 in BAL fluid are significantly lower in animals treated with either 3 mg/kg Dexamethasone (Dex) or 1 mg/kg Fluticasone Propionate (FP). (*p<0.05; **p<0.01; ***p<0.001; ****p<0.0001 compared to the vehicle-control)

BALB/c mice are sensitized with a subcutaneous (SC) administration of 50 µg HDM in CFA on day 0. Mice are then challenged with 50 µg HDM intranasally on Day 14 and endpoints are assessed on day 16. Reference compound and test article treatments are generally administered on or around days 13-16.

Total cells, eosinophils, and neutrophils recovered in broncho-alveolar lavage fluid on day 16 of an HDM-induced severe asthma model. Sensitized and challenged mice demonstrate a significant increase in total inflammatory cells, eosinophils, and neutrophils in BAL fluid. (*p<0.05; ****p<0.0001 compared to the vehicle-control)

Images from control (saline) and severe asthma model (50µg/50µg HDM) BAL fluid. Macrophages (M), Lymphocytes (L), Neutrophils (N), and Eosinophils (E) can all be observed in the BAL fluid from mice in the severe asthma model.

Lung Resistance is measured on day 16 of an HDM-induced severe asthma model, following exposure to increasing doses of methacholine. Animals that are sensitized and challenged with HDM display increased lung resistance in comparison to Naïve animals.

H&E- and PAS-stained lung sections from naïve mice and mice from an HDM-induced severe asthma model on day 16. An increased presence of perivascular and peribronchiolar inflammation (red arrows) is observed in diseased animals. Larger bronchioles of diseased animals are lined with moderate numbers of PAS-positive goblet cells (green arrows) whereas saline control lungs had PAS-negative cells (black arrows).

A mixed Th1/Th2 cytokine inflammatory profile in BAL fluid of diseased animals is observed in a severe asthma phenotype.