Abstract
Asthma exacerbations are severe conditions lacking efficient treatment options. Elevated levels of IL-1β have been associated with frequent exacerbations in both asthmatics and COPD (Juan-Juan F. et al;CHEST 2015;148-3;618-629).We have previously showed a role for TH2 cytokines during asthma exacerbation using our translational mouse model of asthma exacerbation. In the present study we aimed to investigate the role of IL-1β in mediating TH2 immunity during dsRNA-induced exacerbations.
Methods: Wild type (WT) and IL-1β deficient mice (IL-1β-/-) were challenged with HDM to establish allergic airway inflammation followed by dsRNA stimulation for 3 consecutive days to mimic viral-induced asthma exacerbation. Inflammatory cells and total protein were analysed in BALF. Expression of lung tissue cytokines was analysed by RT-qPCR.
Results: HDM challenges induced lung eosinophilia in WT (p<0.01), which was reduced in the IL-1β-/- mice (p=0.055). HDM-induced eosinophilic inflammation persisted at exacerbation in both WT and IL-1β-/-, while dsRNA-induced neutrophilia was reduced in IL-1β-/- mice (p<0.05). Gene expression of TSLP, CCL5 CXCL1 and Muc5ac was induced (p<0.05) at exacerbation in WT mice, while the levels were reduced in IL-1β-/-. CCL2 and CCL11 increased in WT but were not affected in the IL-1β-/-, at exacerbation.
Conclusion: Our data suggest that IL-1β signalling is involved during dsRNA-induced asthma exacerbation by modulating the immune response to reduced lung cytokine levels and dampened recruitment of airway inflammatory cells. This suggests that IL-1β could be a potential pharmacological target for intervention in viral-induced exacerbations of asthma.
- Copyright ©the authors 2016