肿瘤坏死因子（TNF）是一种多效细胞因子，调节许多生理和病理免疫介导的过程。具体而言，它已被认为是一种重要的促炎细胞因子，与多发性硬化症（MS）的发病机制和进展有关。 MS 是一种慢性免疫介导的中枢神经系统疾病，其特征是白质和灰质的多灶性急性和慢性炎症性脱髓鞘，以及神经轴突损失。 MS 研究领域的一个最新概念是由复发活动无关进展 (PIRA) 导致的残疾。 PIRA 认识到自疾病早期阶段以来的残疾积累可能独立于复发活动而发生，克服了多发性硬化症作为复发性炎症或进行性神经退行性疾病的传统二元观点。多项研究表明，急性和慢性活动性多发性硬化症脑损伤中 TNF 表达均上调。此外，在 MS 患者的血清和脑脊液中观察到 TNF 水平升高。 TNF 似乎在维持慢性鞘内炎症、促进轴突损伤神经变性、从而导致疾病进展和残疾积累方面发挥着重要作用。总之，这篇综述强调了目前对 TNF 及其受体在 MS 进展中的理解，特别关注相对未经探索的 PIRA 病症。该领域的进一步研究有望针对 TNF 进行潜在的治疗干预，以减轻多发性硬化症患者的残疾。© 2024。作者。

Tumor necrosis factor (TNF) is a pleiotropic cytokine regulating many physiological and pathological immune-mediated processes. Specifically, it has been recognized as an essential pro-inflammatory cytokine implicated in multiple sclerosis (MS) pathogenesis and progression. MS is a chronic immune-mediated disease of the central nervous system, characterized by multifocal acute and chronic inflammatory demyelination in white and grey matter, along with neuroaxonal loss. A recent concept in the field of MS research is disability resulting from Progression Independent of Relapse Activity (PIRA). PIRA recognizes that disability accumulation since the early phase of the disease can occur independently of relapse activity overcoming the traditional dualistic view of MS as either a relapsing-inflammatory or a progressive-neurodegenerative disease. Several studies have demonstrated an upregulation in TNF expression in both acute and chronic active MS brain lesions. Additionally, elevated TNF levels have been observed in the serum and cerebrospinal fluid of MS patients. TNF appears to play a significant role in maintaining chronic intrathecal inflammation, promoting axonal damage neurodegeneration, and consequently contributing to disease progression and disability accumulation. In summary, this review highlights the current understanding of TNF and its receptors in MS progression, specifically focusing on the relatively unexplored PIRA condition. Further research in this area holds promise for potential therapeutic interventions targeting TNF to mitigate disability in MS patients.© 2024. The Author(s).