Investigating the effects of interleukin-33 on rhinovirus A induced changes in asthmatic bronchial epithelial cells

Rhinovirus (RV) is a major trigger of asthma exacerbations. RV infection of the bronchial epithelium leads to interleukin-33 (IL-33) release, driving local inflammation. The role of IL-33 release in asthmatic airways on virally induced mechanisms in asthma however remains unclear. Our hypotheses were: i) RV can induce inflammation and damage in asthmatic bronchial epithelial cells (HBEC) in vitro and ii) the presence of IL-33 can modify virally induced inflammation and epithelial damage. Cultured HBECs from subjects with asthma (n=13) were exposed to RV (MOI:1), 50ng/ml recombinant IL-33 or both for 24 hours. Levels of IL-33, sST2 (soluble IL-33 receptor), TSLP and CXCL10 in the supernatants were measured as markers of inflammation (Luminex). Lactate dehydrogenase (LDH) activity was assayed as a marker of cell damage. Measurement of IL-33, sST2, CXCL10, TSLP and LDH activity identified heterogeneous responses to RV infection across donors. RV-induced changes in sST2 (fold 1.98) and LDH activity (fold 1.17) were significantly correlated (R2=0.62; p Our findings indicate that the presence of IL-33 can selectively modulate virally induced cell activation and damage in asthmatic HBECs responsive to virus. Ongoing studies aim to define the effect of blocking IL-33 and the effect of IL-33 genetic variants on viral responses, including extensively characterising cellular responses using RNA-seq. Method: AnaptysBio Inc, Medical Research Council UK.