Ballantyne Sarah J, Barlow Jillian L, Jolin Helen E, Nath Puneeta, Williams Alison S, Chung Kian Fan, Sturton Graham, Wong See Heng, McKenzie Andrew N J
Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
J Allergy Clin Immunol. 2007 Dec;120(6):1324-31. doi: 10.1016/j.jaci.2007.07.051. Epub 2007 Sep 24.
IL-25 (IL-17E), a member of the IL-17 family of immunoregulatory cytokines, has been implicated in the regulation of type 2 immunity. Its roles in antigen-driven airway inflammation and airway hyperresponsiveness (AHR) remain to be fully established.
We sought to determine whether a neutralizing antibody against IL-25 represents a novel therapeutic for airway inflammation and hyperresponsiveness.
We generated a neutralizing mAb against IL-25 and used this to inhibit IL-25 in a mouse model of allergic airway disease.
Blocking IL-25 in an experimental model of allergic asthma prevented AHR, a critical feature of clinical asthma. Administration of anti-IL-25 mAb during the sensitization phase resulted in significantly reduced levels of IL-5 and IL-13 production, eosinophil infiltration, goblet cell hyperplasia, and serum IgE secretion, and prevented AHR. Even more striking was the ability of anti-IL-25 mAb, administered only during the challenge phase of the response, specifically to prevent AHR even during an ongoing type 2 inflammatory response in the lungs.
IL-25 is critical for development of AHR.
We define a novel pathway for the induction of AHR and suggest that IL-25 represents an important therapeutic target for the treatment of asthma. Significantly, our antibody also blocks the binding of human IL-25 to its receptor.
白细胞介素-25（IL-17E）是免疫调节细胞因子IL-17家族的成员，与2型免疫调节有关。其在抗原驱动的气道炎症和气道高反应性（AHR）中的作用仍有待充分明确。
我们试图确定抗IL-25中和抗体是否是气道炎症和高反应性的新型治疗方法。
我们制备了一种抗IL-25的中和单克隆抗体，并将其用于在过敏性气道疾病小鼠模型中抑制IL-25。
在过敏性哮喘实验模型中阻断IL-25可预防AHR，这是临床哮喘的一个关键特征。在致敏阶段给予抗IL-25单克隆抗体可显著降低IL-5和IL-13的产生水平、嗜酸性粒细胞浸润、杯状细胞增生以及血清IgE分泌，并预防AHR。更显著的是，仅在反应的激发阶段给予抗IL-25单克隆抗体，即使在肺部正在进行的2型炎症反应期间，也能特异性地预防AHR。
IL-25对AHR的发展至关重要。
我们定义了一种诱导AHR的新途径，并表明IL-25是治疗哮喘的重要治疗靶点。重要的是，我们的抗体还能阻断人IL-25与其受体的结合。
