美国科罗拉多大学丹佛分校Charles A. Dinarello课题组发现，IL-1R3阻断剂可以广泛削弱IL-1家族6个成员的功能，并揭示其在疾病模型中的作用。相关论文于2019年8月19日在线发表于国际学术期刊《自然—免疫学》。

研究人员开发了针对人IL-1R3的阻断性单克隆抗体（MAB-hR3），并且证明该抗体在体外特异性地抑制通过IL-1、IL-33和IL-36的信号传导。此外，在三种不同的体内疾病模型（晶体诱发的腹膜炎、过敏性呼吸道炎症和牛皮癣）中，研究人员发现用单个单克隆抗体靶向小鼠的IL-1R3（MAB-mR3）能够显著减弱不同细胞因子引起的炎症和疾病严重程度。研究人员认为，在由多种细胞因子引起的疾病中，单一拮抗剂如IL-1R3的单克隆抗体是具有良好转化前景的治疗选择。

据介绍，白细胞介素（IL）-1R3是三种信号通路中的共同受体，涉及IL-1家族的六种细胞因子（IL-1α、IL-1β、IL-33、IL-36α、IL-36β和IL-36γ）。在许多疾病中，多种细胞因子促进疾病发生。例如，在哮喘中，IL-33和IL-1都很重要，牛皮癣中的IL-36和IL-1也是如此。

附：英文原文

Title: IL-1R3 blockade broadly attenuates the functions of six members of the IL-1 family, revealing their contribution to models of disease

Author: Jesper Falkesgaard Højen, Marie Louise Vindvad Kristensen, Amy S. McKee, Megan Taylor Wade, Tania Azam, Lars P. Lunding, Dennis M. de Graaf, Benjamin J. Swartzwelter, Michael Wegmann, Martin Tolstrup, Karsten Beckman, Mayumi Fujita, Stephan Fischer, Charles A. Dinarello

Issue&Volume: 19 August 2019

Abstract: Interleukin (IL)-1R3 is the co-receptor in three signaling pathways that involve six cytokines of the IL-1 family (IL-1α, IL-1β, IL-33, IL-36α, IL-36β and IL-36γ). In many diseases, multiple cytokines contribute to disease pathogenesis. For example, in asthma, both IL-33 and IL-1 are of major importance, as are IL-36 and IL-1 in psoriasis. We developed a blocking monoclonal antibody (mAb) to human IL-1R3 (MAB-hR3) and demonstrate here that this antibody specifically inhibits signaling via IL-1, IL-33 and IL-36 in vitro. Also, in three distinct in vivo models of disease (crystal-induced peritonitis, allergic airway inflammation and psoriasis), we found that targeting IL-1R3 with a single mAb to mouse IL-1R3 (MAB-mR3) significantly attenuated heterogeneous cytokine-driven inflammation and disease severity. We conclude that in diseases driven by multiple cytokines, a single antagonistic agent such as a mAb to IL-1R3 is a therapeutic option with considerable translational benefit.

DOI: https://doi.org/10.1038/s41590-019-0467-1

Source: https://www.nature.com/articles/s41590-019-0467-1