Ulhaq Zulvikar Syambani, Zulkarnain Zulkarnain, Istifiani Lola Ayu, Pamungkas Syafrizal Aji, Soeatmadji Djoko Wahono, Aulanni'am Aulanni'am
Research Center for Pre-clinical and Clinical Medicine, National Research and Innovation Agency Republic of Indonesia, Cibinong 16911, Indonesia.
Department of Physiology, Faculty of Medicine, Universitas Syiah Kuala, Banda Aceh 23111, Indonesia.
Endocrinol Diabetes Nutr (Engl Ed). 2025 Aug-Sep;72(7):501598. doi: 10.1016/j.endien.2025.501598.
Excessive inflammatory cytokines are known to impact immune response and autoimmunity. In this study, we quantified the level of interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), glycoprotein 130 (sgp130) and IL-10 to determine their involvement in the pathogenesis of Graves' disease (GD), in addition to the assessment serum cytokines IL-6, sIL-6R, sgp130, and IL-10 performance as biomarkers for the diagnosis of GD.
A total of 20 patients with GD and 21 healthy individuals from the Indonesian population were enrolled. The serum concentrations of the selected cytokines were quantified using the ELISA method. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and TSH receptor antibody (TSHR-Ab) were also evaluated. Comparative analysis was performed in addition to the assessment of the diagnostic performance of cytokines using receiver-operating-curve (ROC) analysis. Pearson's correlation coefficient was used to assess the relationship between 2 quantitative variables.
Patients with GD had a higher IL-6, sIL-6R, and IL-6/IL-10 ratio but a lower sgp130/sIL-6R/IL-6 ratio vs controls. The ROC curve analysis showed that the sgp130/sIL-6R/IL-6 ratio exhibited better performance than IL-6, sIL-6R, and IL-6/IL-10 ratio in diagnosing GD. In addition, serum levels of IL-6, sIL-6, and IL-10 were associated with thyroid parameters, including TSHR-antibody (Ab) levels.
IL-6 trans-signaling and imbalance of inflammatory response could be prominent factors in the pathogenesis of GD.
已知过量的炎性细胞因子会影响免疫反应和自身免疫。在本研究中，我们对白细胞介素（IL）-6、可溶性IL-6受体（sIL-6R）、糖蛋白130（sgp130）和IL-10的水平进行了定量，以确定它们在格雷夫斯病（GD）发病机制中的作用，此外还评估了血清细胞因子IL-6、sIL-6R、sgp130和IL-10作为GD诊断生物标志物的性能。
共纳入20例来自印度尼西亚人群的GD患者和21名健康个体。使用酶联免疫吸附测定（ELISA）方法对所选细胞因子的血清浓度进行定量。还评估了促甲状腺激素（TSH）、游离甲状腺素（FT4）、游离三碘甲状腺原氨酸（FT3）和促甲状腺激素受体抗体（TSHR-Ab）。除了使用受试者工作特征曲线（ROC）分析评估细胞因子的诊断性能外，还进行了比较分析。采用Pearson相关系数评估两个定量变量之间的关系。
与对照组相比，GD患者的IL-6、sIL-6R和IL-6/IL-10比值较高，但sgp130/sIL-6R/IL-6比值较低。ROC曲线分析表明，在诊断GD方面，sgp130/sIL-6R/IL-6比值比IL-6、sIL-6R和IL-6/IL-10比值表现更好。此外，IL-6、sIL-6和IL-10的血清水平与甲状腺参数相关，包括TSHR抗体（Ab）水平。
IL-6转信号传导和炎症反应失衡可能是GD发病机制中的突出因素。
