LPS-challenged equine bronchi: evidence for IL-6 as a target against AHR

Abstract

<b>Background:</b> AHR and inflammation are main characteristics of human and equine asthma. Challenging equine airways with LPS elicits AHR, representing also a suitable model for human airways dysfunction (Pulm Pharmacol Ther. 2018;49:88-94). <b>Aim</b> To match the inflammatory and contractile profile in LPS-challenged equine isolated bronchi to identify molecular targets potentially effective to counteract AHR. <b>Methods</b> Equine isolated bronchi were incubated overnight with LPS (0.1-100 ng/ml). The contractile response to electrical field stimulation (EFS) and levels of cytokines, chemokines, and NKA were quantified. The role of capsaicin sensitive-sensory nerves, NK2 receptor, TRPV1, and epithelium were also investigated. <b>Results</b> LPS 1 ng/ml elicited AHR to EFS (+238.17±25.20% P&lt;0.001). LPS significantly (P&lt;0.05) increased the levels of IL-4 (+36.08±1.62%), IL-5 (+38.60±3.58%), IL-6 (+33.79±2.59%), IL-13 (+40.91±1.93%), IL-1β (+1650.16±71.16%), IL-33 (+88.14±8.93%), TGF-β (22.29±1.03%), TNF-α (+56.13±4.61%), CXCL-8 (+98.49±17.70%), EOTAXIN (+32.26±2.27%), MCP-1 (+49.63±4.59%), (RANTES +36.38±2.24%), and NKA (+112.81±6.42%). Capsaicin sensitive-sensory nerves, NK2 receptor, and TRPV1 were generally involved in the LPS-mediated inflammation. Epithelium modulated the release of IL-1β, IL-33, and TGF-β. Only the levels of IL-6 fitted with EFS-induced AHR, an effect inhibited by anti-IL-6 antibody (P&lt;0.05); exogenous IL-6 induced AHR to EFS similar to that elicited by LPS. <b>Conclusions:</b> Targeting IL-6 may represent an effective strategy to prevent equine AHR, supporting recent evidence on the&nbsp;pivotal role of IL-6 in human severe asthma (Am J Respir Crit Care Med. 2020;1324-1325).