Liu Suling, Cui Yang, Zhang Xiao
Shantou University Medical College, Shantou, Guangdong Province, China.
Department of Rheumatology and Immunology, Guangdong Provincial People's General Hospital, Guangdong Academy of Medical Sciences, No.106 2nd Zhongshan Road, Yuexiu district, Guangzhou, 510080, China.
Clin Rheumatol. 2021 Jan;40(1):25-32. doi: 10.1007/s10067-020-05207-z. Epub 2020 Jun 6.
Iguratimod (IGU) is a novel small molecule anti-rheumatic drug with the effect of non-steroidal anti-inflammatory drug and disease-modifying anti-rheumatic drug. IGU has various mechanisms of action, including inhibition of prostaglandin E2, tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17) production, inhibition of macrophage migration inhibitory factor (MIF)-induced proinflammatory effects, inhibition of osteoclastogenesis, and promotion of osteoblastic differentiation. Ankylosing spondylitis (AS) is the major subtype of spondyloarthritis that affects the axial skeleton, causing inflammatory back pain, which can lead to impairments in structure and function and a decrease in quality of life. Theories on pathogenesis of AS include misfolding of human leukocyte antigen-B27 during its assembly leading to endoplasmic reticulum stress and unfolded protein response (UPR). Activation of UPR genes results in release of TNF-α and IL-17, which have been shown to be important in the development of AS. In addition, current evidence suggests the importance of cyclooxygenase-2/prostaglandin E2 pathway and MIF in the pathogenesis of AS. Current drugs for the treatment of AS are limited and exploration of effective drugs is needed. IGU may be effective for the treatment of AS given that its mechanisms of action are closely related to the pathogenesis of AS. In fact, several small-scale clinical trials have shown the efficacy of IGU for the treatment of AS. This article reviews the molecular mechanisms of IGU that are related to the pathogenesis of AS and clinical trials of IGU for the treatment of AS, providing a reference for future clinical application of IGU for AS.
艾拉莫德（IGU）是一种新型小分子抗风湿药物，具有非甾体抗炎药和改善病情抗风湿药的作用。IGU具有多种作用机制，包括抑制前列腺素E2、肿瘤坏死因子-α（TNF-α）、白细胞介素-17（IL-17）的产生，抑制巨噬细胞移动抑制因子（MIF）诱导的促炎作用，抑制破骨细胞生成，并促进成骨细胞分化。强直性脊柱炎（AS）是脊柱关节炎的主要亚型，影响中轴骨骼，引起炎性背痛，可导致结构和功能受损以及生活质量下降。AS的发病机制理论包括人类白细胞抗原-B27在组装过程中错误折叠导致内质网应激和未折叠蛋白反应（UPR）。UPR基因的激活导致TNF-α和IL-17的释放，已证明它们在AS的发展中起重要作用。此外，目前的证据表明环氧化酶-2/前列腺素E2途径和MIF在AS发病机制中的重要性。目前用于治疗AS的药物有限，需要探索有效的药物。鉴于IGU的作用机制与AS的发病机制密切相关，它可能对AS治疗有效。事实上，几项小规模临床试验已显示IGU治疗AS的疗效。本文综述了IGU与AS发病机制相关的分子机制以及IGU治疗AS的临床试验，为IGU未来在AS临床应用中提供参考。
