Bahn R S
Division of Endocrinology, Mayo Clinic/Foundation, Rochester, Minnesota 55905, USA.
Thyroid. 1998 May;8(5):415-8. doi: 10.1089/thy.1998.8.415.
Interactions between between orbital fibroblasts and immunocompetent cells that infiltrate or reside within the orbit are thought to be important in the pathogenesis of thyroid eye disease (TED). These interactions are mediated primarily by cytokines; interferon-gamma, tumor necrosis factor-alpha, interleukin-1alpha and leukoregulin are of particular interest in this regard. These mediators induce or enhance the in vitro expression of immunomodulatory proteins in orbital fibroblasts, and stimulate proliferative and metabolic activities of these cells. The stimulation by particular cytokines of glycosaminoglycan synthesis in orbital fibroblasts is an important factor in the development of the clinical disease. A similarly important pathophysiological role for cytokines has been defined in rheumatoid arthritis. In this disease, the chronic erosive changes in the cartilage and bone of the joints result from cytokine-stimulated production of collegenases and other neutral proteases by synovial cells and articular chondrocytes. Advances in the understanding of the pathogenesis of rheumatologic joint disease has led to treatment trials aimed at immune-modulation, including trials of anticytokine therapy. Lessons learned in early clinical trials using these biological therapies in the treatment of rheumatoid arthritis can be applied to studies of similar agents in the treatment of TED.
眼眶成纤维细胞与浸润或存在于眼眶内的免疫活性细胞之间的相互作用被认为在甲状腺眼病（TED）的发病机制中起重要作用。这些相互作用主要由细胞因子介导；在这方面，γ干扰素、肿瘤坏死因子-α、白细胞介素-1α和白细胞调节素尤其受到关注。这些介质诱导或增强眼眶成纤维细胞中免疫调节蛋白的体外表达，并刺激这些细胞的增殖和代谢活动。特定细胞因子对眼眶成纤维细胞中糖胺聚糖合成的刺激是临床疾病发展的一个重要因素。细胞因子在类风湿性关节炎中也被定义了类似重要的病理生理作用。在这种疾病中，关节软骨和骨骼的慢性侵蚀性变化是由细胞因子刺激滑膜细胞和关节软骨细胞产生胶原酶和其他中性蛋白酶所致。对风湿性关节病发病机制认识的进展导致了旨在免疫调节的治疗试验，包括抗细胞因子治疗试验。在早期临床试验中使用这些生物疗法治疗类风湿性关节炎所吸取的经验教训可应用于TED治疗中类似药物的研究。
