Chen Po-Ku, Wey Shiow-Jiuan, Chen Der-Yuan
Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan.
College of Medicine, China Medical University, Taichung, Taiwan.
Expert Rev Clin Immunol. 2022 Aug;18(8):823-833. doi: 10.1080/1744666X.2022.2096592. Epub 2022 Jul 4.
Adult-onset Still's disease (AOSD) is an autoinflammatory disease driven by the innate immune response. Given the ambiguity in clinical presentation and lack of specific diagnostic biomarkers, AOSD diagnosis is usually delayed in the early stage. Because AOSD is a rare disease with clinical heterogeneity, there is no consensus on its treatment currently. This review summarizes the current research evidence regarding the pathogenic role and the diagnostic or therapeutic potential of interleukin (IL)-18 in AOSD.
We searched the MEDLINE database using the PubMed interface and reviewed English-language literature from 1971 to 2022. This review focusing on IL-18 discusses its pathogenic role and clinical implications in AOSD.
NLRP3-inflammasome activation with IL-18 overproduction plays a pathogenic role in AOSD. IL-18 is closely linked to the clinical manifestations and disease activity of AOSD and may be a diagnostic biomarker. Given its pathogenic role in AOSD, IL-18 could become a potential therapeutic target. IL-18 binding protein (IL-18BP) negatively regulates the biological activity of IL-18 by inhibiting IL-18 signaling, and a clinical trial revealed that IL-18BP (Tadekinig alfa) treatment was well-tolerated and effective for AOSD. Recently, monoclonal antibodies against IL-18 have been under evaluation in a phase 1b trial.
成人斯蒂尔病（AOSD）是一种由先天性免疫反应驱动的自身炎症性疾病。鉴于临床表现不明确且缺乏特异性诊断生物标志物，AOSD在早期诊断通常会延迟。由于AOSD是一种具有临床异质性的罕见疾病，目前关于其治疗尚无共识。本综述总结了目前关于白细胞介素（IL）-18在AOSD中的致病作用以及诊断或治疗潜力的研究证据。
我们使用PubMed界面搜索了MEDLINE数据库，并回顾了1971年至2022年的英文文献。本综述聚焦于IL-18，讨论了其在AOSD中的致病作用和临床意义。
NLRP3炎性小体激活伴IL-18过度产生在AOSD中起致病作用。IL-18与AOSD的临床表现和疾病活动密切相关，可能是一种诊断生物标志物。鉴于其在AOSD中的致病作用，IL-18可能成为潜在的治疗靶点。IL-18结合蛋白（IL-18BP）通过抑制IL-18信号传导负调节IL-18的生物学活性，一项临床试验显示IL-18BP（他地尼单抗）治疗耐受性良好且对AOSD有效。最近，抗IL-18单克隆抗体正在1b期试验中进行评估。
