Rhinovirus-induced bronchial mucosal inflammatory response in asthma

Rationale: Asthma exacerbations are associated with rhinovirus (RV) infection, but the underlying airway inflammatory response is poorly understood. We reported previously that RV infection increases bronchial mucosal TLR-3 expression and neutrophilia in asthma. However, the response of other phenotypes of inflammatory cell to RV infection remains unclear. Methods: We used immunohistochemistry to determine the density of all inflammatory cells (CD45+), and CD3+, CD4+, CD8+, CD20+, CD68+ and tryptase+ mast cells. We counted their numbers in the bronchial mucosa after experimental RV infection of 10 atopic asthmatic (A) and 15 non-atopic normal volunteers (N). We determined the relationship between cell numbers and virus load, PC10 & 20, FEV1% and peak expiratory flow (PEF %). Results: the counts are expressed as median (range) /1mm2 of subepithelium (Sub) and /0.1 mm2 epithelium (Ep). By comparison to their baseline values, only the numbers of Sub CD68+ cells of both normal [baseline: 146(14-421) vs day 4: 285(96-825), p < 0.02] and asthmatics [baseline: 346(44-600) vs day 4: 546(153-1482), p < 0.01] were significantly increased at day 4 of infection. In all subjects taken together there were significant positive correlations between BAL virus load and Sub CD45+ (r = 0.5, p< 0.03) and CD68+ (r = 0.53, p< 0.05) cells and an inverse correlation between the fall (maximum taken for each subject) in FEV1% and CD4+ cells (r= -0.53, p=0.01). In the A subjects alone BAL virus load correlated significantly with Sub CD20+ cells (r= 0.72, p=0.03).The overall fall from baseline to infection in PC10 histamine correlated inversely with Sub CD3+ (r= -0.75, p=0.02), CD4+ (r= -0.67, p<0.03) and CD8+ (r= -0.65, p= 0.03) cells and that for PC20 was inversely associated with Sub CD20+ cells (r= -0.65, p=0.03). The fall in FEV1 (%) correlated inversely with Ep CD8+ cells (r = -0.72, p= 0.03). The maximum % fall in PEF correlated positively with Sub mast cells (r= 0.8, p=0.03). Conclusion: RV-induced bronchial CD68+ cells are positively associated with BAL virus load. In asthmatics, the numbers of CD4+ and CD8+ T and CD20+ B lymphocytes present during infection are related to increased airway hyperresponsiveness, whereas the numbers of CD4+ and CD8+ T lymphocyte relate to reductions in lung function. Mast cells appeared ‘protective’ as they were positively related to improvements in lung function.