Kinetics of an asthma exacerbation in the mouse model

Asthma exacerbations are a distinct clinical manifestation in the course of the chronic disease. Exacerbations are defined as acute episodes of progressive worsening in shortness of breath, cough, wheezing, and chest tightness or some combination of these symptoms according to the GINA guidelines. They are often related to unscheduled visits of physicians, emergency department visits or hospitalization and require systemic use of corticosteroids and short-acting β-agonists. Therefore the ecological and social burden, as they cause major health care costs and indirect costs due to lost productivity, is high. Epidemiologic studies suggest respiratory viruses as the most prevalent triggers of acute asthma exacerbations.

So our aim is to analyse the viral-induced specific cytokine immune response in asthmatic mice to foresee upcoming acute exacerbations and be able to intervene earlier. For this purpose, we induced asthma by sensitising and challenging female C57BL/6 mice to ovalbumin (OVA). Afterwards, viral infection was reflected by local application of the synthetic dsRNA-analogue poly(I:C) following the last OVA-challenge. We analysed leukocyte numbers in the BAL and the expression of various cytokines, chemokines and immuno-modulatory factors from 2 to 24 hours after poly(I:C) application. Poly(I:C) treatment triggered an acute exacerbation of experimental asthma by point of airway inflammation, mucus production, and airway hyperresponsiveness over time. This was accompanied by steadily increasing levels of several cytokines, such as interferons, pro-inflammatory, T_H2 and T_H17 cytokines as well as chemokines compared to the control groups. So it seems that an early increased combined anti-viral and asthmatic immune response trigger acute asthma exacerbation.