Development of a mouse model mimicking key aspects of a viral asthma exacerbation

Viral respiratory tract infections are known triggers of asthma exacerbations in both adults and children. Current standard of care (inhaled corticosteroids (CS) and long-acting β2-adrenoceptor agonists (LABA)) fails to prevent the loss of control that manifests as an exacerbation. In order to better understand the mechanisms underlying viral asthma exacerbations we established an in vivo model using the clinically-relevant aeroallergen house dust mite (HDM) and the viral mimetic / TLR3 agonist poly I:C. Poly I:C-alone induced a similar neutrophilic inflammatory profile in the bronchoalveolar lavage (BAL) to that of human rhinovirus 1b-alone, accompanied by both elevated BAL KC and IL-1β. When HDM allergic mice were also challenged with poly I:C the neutrophilic inflammatory profile was exacerbated. Increased CD8+ T-cell numbers along with increased CD4+ and CD8+ activation were also observed along with elevated KC and IL-1β. No increases in Th2 cytokines, or the eosinophil chemoattractant CCL11, above those induced by HDM-alone were observed. The poly I:C-exacerbated neutrophilia did not translate to changes in airways hyperresponsiveness (AHR) indicating that in this model inflammation and AHR are two mechanistically independent events. To test the clinical relevance of this model CS sensitivity was assessed using prednisone, a synthetic oral CS used to manage exacerbations in asthmatics already on maximal doses of inhaled CS. Th...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research