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, TH2 and TH17 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.