Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Mol Neurobiol. 2022 Mar;59(3):1724-1743. doi: 10.1007/s12035-022-02725-6. Epub 2022 Jan 11.
Increasing evidence corroborates the fundamental role of neuroinflammation in the development of epilepsy. Proinflammatory cytokines (PICs) are crucial contributors to the inflammatory reactions in the brain. It is evidenced that epileptic seizures are associated with elevated levels of PICs, particularly interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), which underscores the impact of neuroinflammation and PICs on hyperexcitability of the brain and epileptogenesis. Since the pathophysiology of epilepsy is unknown, determining the possible roles of PICs in epileptogenesis could facilitate unraveling the pathophysiology of epilepsy. About one-third of epileptic patients are drug-resistant, and existing treatments only resolve symptoms and do not inhibit epileptogenesis; thus, treatment of epilepsy is still challenging. Accordingly, understanding the function of PICs in epilepsy could provide us with promising targets for the treatment of epilepsy, especially drug-resistant type. In this review, we outline the role of neuroinflammation and its primary mediators, including IL-1β, IL-1α, IL-6, IL-17, IL-18, TNF-α, and interferon-γ (IFN-γ) in the pathophysiology of epilepsy. Furthermore, we discuss the potential therapeutic targeting of PICs and cytokine receptors in the treatment of epilepsy.
越来越多的证据证实了神经炎症在癫痫发生中的基本作用。促炎细胞因子（PICs）是大脑炎症反应的关键贡献者。有证据表明，癫痫发作与 PICs 水平升高有关，特别是白细胞介素-1β（IL-1β）、IL-6 和肿瘤坏死因子-α（TNF-α），这强调了神经炎症和 PICs 对大脑过度兴奋和癫痫发生的影响。由于癫痫的病理生理学尚不清楚，确定 PICs 在癫痫发生中的可能作用有助于揭示癫痫的病理生理学。大约三分之一的癫痫患者对药物有抗药性，现有的治疗方法只能缓解症状，不能抑制癫痫发生；因此，治疗癫痫仍然具有挑战性。因此，了解 PICs 在癫痫中的作用可以为我们提供治疗癫痫的有希望的靶点，特别是耐药型。在这篇综述中，我们概述了神经炎症及其主要介质（包括 IL-1β、IL-1α、IL-6、IL-17、IL-18、TNF-α 和干扰素-γ（IFN-γ））在癫痫发病机制中的作用。此外，我们还讨论了针对 PICs 和细胞因子受体的潜在治疗靶点在癫痫治疗中的应用。
