Abstract
The pathogenic mechanisms of rhinovirus-induced asthma exacerbations are incompletely understood. Impaired production of innate IFN-β and IFN-λ have been identified in bronchial epithelial cells and bronchoalveloar lavage macrophages from atopic mild moderate asthmatics upon rhinovirus infection in vitro. These cells display similar production of pro-inflammatory cytokines when compared to cells cultured from non-asthmatic, non-atopic individuals, and are observable in steroid treated and steroid naive individuals. In the present study, bronchial epithelial cells were cultured from severe asthmatic children (n=8, mean age 11yr, range 9-15, 63% male) and non-atopic non-asthmatic controls (n=10, mean age 7yr, range 2-15, 70% male). Cells were infected with RV1B, RV16, or medium and mRNA, protein and virus release was measured at 8-48h post infection. Cells from severe asthmatic children displayed significantly reduced IFN-β (p<0.05) IFN-λ1 (p<0.05) and IFN-λ2/3 mRNA (p<0.05), but not IL-8 (p>0.05) or ENA-78 (p>0.05) compared to controls. Cells cultured from severe asthmatics had significantly higher RV1B (p<0.01), RV16 (p<0.05) release at 48h, compared to controls. Impaired RV1B induced IFN-β and IFN-λ2/3 also showed strong negative correlations with increased virus load (r=-0.79, p=0.013 and r=-0.65, p=0.015 respectively). RV1B induced IFN-λ2/3 from severe asthmatics also showed strong negative correlations with total serum IgE (r=-0.75, p=0.04) and a trend for a negative correlation with total number of positive RAST tests which was not significant (r=-0.69, p=0.06). This is the first report of impaired IFN in severe asthma, and support the previous findings of impaired IFN production in asthmatics.
- © 2011 ERS
