A role for anti-IL33 strategies to limit the epithelial rhinoviral response?

IL33 is a key cytokine driving amplification of type-2 inflammation during airway rhinovirus infection. This study aimed to i) characterise the primary human bronchial epithelial cell (HBEC) response to rhinovirus (RV16) in an IL33 rich environment, ii) determine the effect of anti-IL33 antibodies on RV response and iii) determine the effects of IL33 receptor (IL1RL1) coding variation on findings. <bold>Method:</bold> HBECs were pre-treated with 0.1-10mg/ml of anti-IL33 (Etokimab or Invivogen) antibodies or PBS vehicle control for 1hr, followed by a 24hr challenge with RV (MOI:1), 50ng/ml IL33 or both. Secreted protein (IL33, IL8, TSLP, CXCL10) were determined using Luminex. <bold>Results:</bold> RV induced release of IL33. All stimulations resulted in elevated IL8 release in an additive manner. Exogenous IL33 was needed for significant release of TSLP over baseline post RV. RV induced CXCL10 release. Anti-IL33 blocking attenuated IL8 secretion in an IL33 rich environment with and without RV infection, while RV16+IL33 induced TSLP secretion. Blocking IL33 did not impact RV induced CXCL10 release. IL1RL1 genotype influenced both mediator release and blocking effects. <bold>Conclusion:</bold> RV infection of airway epithelial cells in an IL33 high environment drives amplified inflammation including IL8 and TSLP. Anti-IL33 directly targets RV effects on HBEC particularly in carriers of the IL1RL1 asthma genotype.