Multiple sclerosis (MS) is a common neurological disorder of putative autoimmune origin. Clinical and experimental studies delineate abnormal expression of specific cytokines over the course of the disease. One major cytokine that has been shown to play a pivotal role in MS is tumor necrosis factor (TNF). TNF is a pleiotropic cytokine regulating many physiological and pathological functions of both the immune system and the central nervous system (CNS). Convincing evidence from studies in human and experimental MS have demonstrated the involvement of TNF in various pathological hallmarks of MS, including immune dysregulation, demyelination, synaptopathy and neuroinflammation. However, due to the complexity of TNF signaling, which includes two-ligands (soluble and transmembrane TNF) and two receptors, namely TNF receptor type-1 (TNFR1) and type-2 (TNFR2), and due to its cell- and context-differential expression, targeting the TNF system in MS is an ongoing challenge. This review summarizes the evidence on the pathophysiological role of TNF in MS and in different MS animal models, with a special focus on pharmacological treatment aimed at controlling the dysregulated TNF signaling in this neurological disorder.

中文翻译：

---

重新检查TNF在MS发病机理和治疗中的作用

多发性硬化症（MS）是常见的推定自身免疫性疾病的神经系统疾病。临床和实验研究描述了在疾病过程中特定细胞因子的异常表达。已显示在MS中起关键作用的一种主要细胞因子是肿瘤坏死因子（TNF）。TNF是一种多效细胞因子，可调节免疫系统和中枢神经系统（CNS）的许多生理和病理功能。来自人类和实验性MS的研究的令人信服的证据表明TNF参与了MS的各种病理特征，包括免疫失调，脱髓鞘，突触病和神经炎症。但是，由于TNF信号的复杂性，其中包括两个配体（可溶性和跨膜TNF）和两个受体，即TNF受体1型（TNFR1）和2型（TNFR2），由于其细胞和背景差异表达，靶向MS中的TNF系统是一个持续的挑战。这篇综述总结了TNF在MS和不同MS动物模型中的病理生理作用的证据，特别侧重于旨在控制该神经系统疾病中TNF信号失调的药物治疗。