| Background: The mouse is the most widely used animal model for studying the development of allergic asthma, especially in early life. However, age-dependent allergen responses in these models are understudied.;Objective: The goal of this study was to determine the degree of reactivity of 3-month-old and 9-month-old female C57 Black/6 mice exposed to house dust mite, a ubiquitous allergen and one of the most common triggers of allergic asthma.;Methods: 3-month-old and 9-month-old female C57 Black/6 mice (n=11/age) were randomized into two groups that were treated with house dust mite or phosphate buffered saline (control) via intranasal instillation on days 1, 3, and 5 (sensitization phase). Mice were then treated with house dust mite on days 12, 13, and 14 (challenge phase). On day 15, the mice underwent pulmonary function tests and methacholine challenge to measure changes in airway sensitivity, which was measures as EC200RL (effective concentration that leads to a two-fold increase in airway resistance). Bronchoalveolar lavage fluid was collected for cell differentials. Right lung lobes were fixed, sectioned, and stained for histopathology and immunohistochemistry.;Results: 9-month-old mice exposed to house dust mite had significantly decreased inspiratory capacity and compliance, and increased elastance and small airway/peripheral tissue resistance compared to control. EC200RL in 9-month-old mice was also significantly decreased, reflecting airway hyperresponsiveness. In contrast, 3-month-old mice exposed to house dust mite had no significant changes in lung function. Both age groups demonstrated a strong inflammatory/allergic response to house dust mite: they had significantly increased numbers of monocytes, neutrophils, lymphocytes, and eosinophils compared to their respective PBS groups, although significantly more so in the 9-month-old mice for neutrophils. Lungs of house dust mite treated mice showed marked bronchiolar and perivascular inflammation in contrast to the lungs of the PBS control groups. The bronchiolitis and perivasculitis were more severe in 9-month-old compared to 3-month-old mice exposed to house dust mite.;Conclusion: Sensitization and challenge with house dust mite created a significant airway hyperresponsiveness in 9-month-old female C57 Black/6 mice, but not in 3-month-old female mice. Both ages demonstrated lung inflammation. Bronchiolitis and perivasculitis were more severe in lung sections of 9-month-old mice treated with HDM compared to 3-month-old treated mice. Immunostaining for IL-4, IL-13, and Eotaxin-1 was positive to a greater extent for the 9-month-old mice treated with HDM compared to all other age and treatment groups. The findings of this age-based model may lead to a better understanding of the influence of age on immune-based allergic development of asthmatic-like symptoms and importance of age related Th2-mediated mechanisms that could explain adult-onset asthma. |
