Department of Rheumatology & Immunology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Front Immunol. 2022 Feb 10;13:818413. doi: 10.3389/fimmu.2022.818413. eCollection 2022.
Axial spondyloarthritis (axSpA) is comprised of ankylosing spondylitis (AS) and non-radiographic axSpA. In recent years, the involvement of the interleukin (IL)-23/IL-17 axis in the pathophysiology of axSpA has been widely proposed. Since IL-23 is an upstream activating cytokine of IL-17, theoretically targeting IL-23 should be effective in axSpA, especially after the success of the treatment with IL-17 blockers in the disorder. Unfortunately, IL-23 blockade did not show meaningful efficacy in clinical trials of AS. In this review, we analyzed the possible causes of the failure of IL-23 blockers in AS: 1) the available data from an animal model is not able to support that IL-23 is involved in a preclinical rather than clinical phase of axSpA; 2) Th17 cells are not principal inflammatory cells in the pathogenesis of axSpA; 3) IL-17 may be produced independently of IL-23 in several immune cell types other than Th17 cells in axSpA; 4) no solid evidence supports IL-23 as a pathogenic factor to induce enthesitis and bone formation. Taken together, IL-23 is not a principal proinflammatory cytokine in the pathogenesis of axSpA.
中轴型脊柱关节炎（axSpA）包括强直性脊柱炎（AS）和非放射学 axSpA。近年来，白细胞介素（IL）-23/IL-17 轴在 axSpA 发病机制中的作用已被广泛提出。由于 IL-23 是 IL-17 的上游激活细胞因子，理论上靶向 IL-23 应该对 axSpA 有效，特别是在 IL-17 阻滞剂治疗该疾病取得成功之后。不幸的是，IL-23 阻断剂在 AS 的临床试验中并未显示出有意义的疗效。在这篇综述中，我们分析了 IL-23 阻滞剂在 AS 中失败的可能原因：1）来自动物模型的现有数据无法支持 IL-23 参与 axSpA 的临床前阶段而非临床阶段；2）Th17 细胞不是 axSpA 发病机制中的主要炎症细胞；3）IL-17 可能在 axSpA 中的 Th17 细胞以外的几种免疫细胞类型中独立于 IL-23 产生；4）没有确凿的证据支持 IL-23 作为诱导附着点炎和骨形成的致病因素。综上所述，IL-23 不是 axSpA 发病机制中的主要促炎细胞因子。
