Data_Sheet_2_Mechanisms of Tumor Necrosis Factor-Alpha Inhibitor-Induced Systemic Lupus Erythematosus.pdf

Systemic lupus erythematosus induced by biologics mainly results from tumor necrosis factor-alpha remains unclear. The objectives of the study were to investigate the mechanisms of tumor necrosis factor-alpha inhibitor-induced systemic lupus erythematosus. Peripheral blood mononuclear cells obtained from thirteen psoriasis patients were cultured and treated with the following: untreated control, Streptococcus pyogenes with or without different biologics. The supernatants were collected for cytokines assay. Analysis of cytokine expression revealed that IL-2 and IL-10 levels decreased only in the TNF-α inhibitor-treated groups but not in the groups treated with biologics involving IL-17, IL-12/IL-23 or IL-23 inhibitor mechanisms (p < 0.001, p < 0.05). The IFN-γ/IL-13 ratio increased significantly in patients with SLE inducing biologics to S. pyogenes induction only compared with non-SLE inducing biologics to S. pyogenes induction only (p = 0.001). IL-2 and IL-10 depletion and a shift to the Th-1 pathway in the innate response are the correlated mechanism for tumor necrosis factor-alpha inhibitor-induced systemic lupus erythematosus.

生物制剂诱导的系统性红斑狼疮（SLE）主要由肿瘤坏死因子-α引起，其具体机制尚不明确。本研究旨在探究肿瘤坏死因子-α抑制剂诱导的系统性红斑狼疮的发病机制。研究人员从十三位银屑病患者的外周血中分离出单核细胞，并进行培养和以下处理：未处理的对照组、链球菌A组菌（Streptococcus pyogenes）与不同生物制剂的联合处理。收集上清液进行细胞因子检测。细胞因子表达分析显示，仅在肿瘤坏死因子-α抑制剂处理组中观察到IL-2和IL-10水平降低，而在涉及IL-17、IL-12/IL-23或IL-23抑制剂机制的生物制剂处理组中并未观察到此现象（p < 0.001, p < 0.05）。与仅诱导SLE的生物制剂相比，仅诱导SLE的生物制剂与链球菌A组菌诱导的生物制剂相比，IFN-γ/IL-13比值显著增加（p = 0.001）。IL-2和IL-10的耗竭以及向Th-1途径的转换，是肿瘤坏死因子-α抑制剂诱导的系统性红斑狼疮的关联机制。