Murdock Jennifer, Nguyen John, Hurtgen Brady J, Andorfer Cathy, Walsh John, Lin Andrea, Tubbs Christopher, Erickson Kristine, Cockerham Kimberly
Oculofacial Plastic Surgery, Miami, FL, United States.
Thrive Health, West Vancouver, BC, Canada.
Front Ophthalmol (Lausanne). 2025 Apr 14;5:1544436. doi: 10.3389/fopht.2025.1544436. eCollection 2025.
Elevated serum interleukin-6 (IL-6) levels have been shown to correlate with disease activity in patients with thyroid eye disease (TED), a complex, heterogeneous, autoimmune disease affecting thousands of people worldwide. IL-6 plays a pivotal role in the pathogenesis of TED through three key mechanisms that together may contribute to inflammation, tissue expansion, remodeling, and fibrosis within the orbit. First, IL-6 drives an autoimmune response targeting the thyroid-stimulating hormone receptor (TSHR) by promoting the production of autoantibodies (i.e. TSHR-Ab, TSI), thereby triggering TSHR-dependent immune pathways. Second, IL-6 stimulates the activation and differentiation of orbital fibroblasts, which contributes to the inflammatory process and increase adipogenesis. Finally, IL-6 stimulates T-cell-mediated inflammation, amplifying the immune response within orbital tissues. Although corticosteroids and surgery have served as mainstays of TED treatment, a multimodal approach is often required due to the disease's heterogeneous presentation and response to current treatment options. TED is a chronic, lifelong condition characterized by periods of exacerbation and remission, with inflammation playing a central role in disease progression and severity. Because inflammation can flare intermittently throughout a patient's life, there is growing interest in targeting specific components of the immune system to reduce disease activity and severity. This review focuses on the current evidence supporting IL-6 as a key mediator of TED pathogenesis and explores its potential as a diagnostic biomarker and therapeutic target of the disease.
血清白细胞介素-6（IL-6）水平升高已被证明与甲状腺眼病（TED）患者的疾病活动相关，TED是一种复杂的、异质性的自身免疫性疾病，影响着全球数千人。IL-6通过三种关键机制在TED的发病机制中起关键作用，这三种机制共同作用可能导致眼眶内的炎症、组织扩张、重塑和纤维化。首先，IL-6通过促进自身抗体（即促甲状腺激素受体抗体、促甲状腺素）的产生，驱动针对促甲状腺激素受体（TSHR）的自身免疫反应，从而触发TSHR依赖性免疫途径。其次，IL-6刺激眼眶成纤维细胞的激活和分化，这有助于炎症过程并增加脂肪生成。最后，IL-6刺激T细胞介导的炎症，放大眼眶组织内的免疫反应。尽管皮质类固醇和手术一直是TED治疗的主要手段，但由于该疾病的异质性表现以及对当前治疗方案的反应，通常需要采用多模式方法。TED是一种慢性的、终身性疾病，其特征是病情有加重和缓解期，炎症在疾病进展和严重程度中起核心作用。由于炎症在患者一生中可能会间歇性发作，因此人们越来越关注针对免疫系统的特定成分来降低疾病活动度和严重程度。本综述重点关注支持IL-6作为TED发病机制关键介质的现有证据，并探讨其作为该疾病诊断生物标志物和治疗靶点的潜力。
