Crucial timing of a viral component exposure to exacerbate allergen-induced asthma

Background: Viral infection is one of the causes to exacerbate asthma. It has not been elucidated fully that the virus-induced asthma exacerbation is occurred either during allergen exposure or after establishment of asthma. Therefore, to know when virus infection could be effective to induce asthma exacerbation is important for clarification of the pathogenesis. Objective : To investigate the effects of virus infection, we employed allergic asthma mice which were exposed with a viral component with changing the timing of the administration. Methods: Wild-type C57BL/6 mice were sensitized (days 0 and 14) and challenged (days 28-30) with ovalbumin (OVA), and airway hyperresponsiveness (AHR) and airway inflammation were analyzed 72 hours after final OVA challenge. A synthesized double-stranded (ds) RNA, poly I:C which mimics a viral component, was administered intratracheally during OVA challenge (days 28-30) or after OVA challenge (day 32), indicating during or after development of asthma, respectively. Results: Treatment with poly I:C during OVA challenge inhibited the development of airway eosinophilia and production of Th2 cytokines such as IL-4, IL-5, and IL-13 in the lung. On the other hand, poly I:C when given after OVA challenge, induced severe AHR, airway inflammation with mixture of eosinophilia and neutrophilia, and increase levels of IFN-γ and IL-17 with keeping Th2 cytokine levels. Conclusions: These data suggest a virus component dsRNA exposure, not during development of asthma but after establishment of asthma, is capable of contributing to the asthma exacerbation with airway neutrophilia and pulmonary Th1/Th17 cytokine storm that are suggested to be associated with severe asthma.