Early Production of IL-6, KC, and TNF is Involved in the Virus-Induced Exacerbation of Experimental Asthma in Mice

Epidemiologic studies suggest respiratory viral infections as a major trigger for acute exacerbation of chronic asthma. Defined as acute episodes of progressive worsening of disease symptoms, they lead to unscheduled visits of physicians, emergency departments or hospitalization and the requirement of increased and/or systemic corticosteroids. So, an early detection of upcoming exacerbations is needed for prevention and early countermeasures. Thus, our aim is to analyse the early virus-induced specific immune response in asthmatic mice. An established mouse model of experimental asthma exacerbation was used. Experimental asthma was induced in female C57BL/6 mice by systemic sensitization to and challenge with ovalbumin. Acute exacerbation was induced with intra-nasal application of the synthetic dsRNA-analogue poly(I : C). Analysis of leukocyte numbers in broncho-alveolar lavage (BAL) and the expression and production of various cytokines, chemokines, and immuno-modulatory factors in different compartments from 0 to 96 hours after poly(I : C) application were performed. Eosinophils show an early and continuing influx throughout time, whereas neutrophils show an early and time depending increasing influx with peaking numbers at 12 hours. Accompanying this, chemokines like eotaxin and KC were released. Furthermore, type I and type III interferons and proinflammatory cytokines like Interleukin (IL) 1 and tumor necrosis factor (TNF) were released early and continuing, whereas T helper 2 (TH2) cell cytokines were only moderately increased. Lastly, we found very high and remaining levels of IL-6 in BAL, nasal lavage, and serum already 2 hours until 12 hours after poly(I : C) application.