Unit of Neurology and Neurorehabilitation, IRCCS Neuromed, Pozzilli (IS), Italy.
Tor Vergata University, Department of Systems Medicine, Via Montpellier 1, Rome, Italy.
Neurorehabil Neural Repair. 2019 Oct;33(10):825-835. doi: 10.1177/1545968319868713. Epub 2019 Aug 20.
Synaptic plasticity helps in reducing the clinical expression of brain damage and represents a useful mechanism to compensate the negative impact of new brain lesions in multiple sclerosis (MS). Inflammation, altering synaptic plasticity, could negatively influence the disease course in relapsing-remitting MS (RR-MS). In the present study, we explored whether interleukin (IL)-6, a major proinflammatory cytokine involved in MS pathogenesis, alters synaptic plasticity and affects the ability to compensate for ongoing brain damage. The effect of IL-6 incubation on long-term potentiation (LTP) induction was explored , in mice hippocampal slices. We also explored the correlation between the cerebrospinal fluid (CSF) levels of this cytokine and the LTP-like effect induced by the paired associative stimulation (PAS) in a group of RR-MS patients. Finally, we examined the correlation between the CSF levels of IL-6 at the time of diagnosis and the prospective disease activity in a cohort of 150 RR-MS patients. LTP induction was abolished by IL-6. Consistently, in patients with MS, a negative correlation emerged between IL-6 CSF concentrations and the effect of PAS. In MS patients, longer disease duration before diagnosis was associated with higher IL-6 CSF concentrations. In addition, elevated CSF levels of IL-6 were associated with greater clinical expression of new inflammatory brain lesions, unlike in patients with low or absent IL-6 concentrations, who had a better disease course. IL-6 interfering with synaptic plasticity mechanisms may impair the ability to compensate the clinical manifestation of new brain lesions in RR-MS patients.
突触可塑性有助于减轻脑损伤的临床表现，是补偿多发性硬化症（MS）中新生脑损伤负面影响的有用机制。炎症改变突触可塑性，可能会对缓解复发型 MS（RR-MS）的病程产生负面影响。在本研究中，我们探讨了白细胞介素（IL）-6 作为参与 MS 发病机制的主要促炎细胞因子，是否会改变突触可塑性并影响补偿持续脑损伤的能力。我们在小鼠海马切片中探索了 IL-6 孵育对长时程增强（LTP）诱导的影响。我们还探讨了该细胞因子的脑脊液（CSF）水平与 RR-MS 患者中配对关联刺激（PAS）诱导的 LTP 样效应之间的相关性。最后，我们在 150 例 RR-MS 患者队列中检查了诊断时 CSF 中 IL-6 水平与前瞻性疾病活动之间的相关性。IL-6 可消除 LTP 的诱导。同样，在 MS 患者中，IL-6CSF 浓度与 PAS 效应之间出现了负相关。在 MS 患者中，诊断前疾病持续时间较长与 CSF 中 IL-6 浓度升高相关。此外，与 CSF 中 IL-6 浓度较低或不存在的患者相比，CSF 中升高的 IL-6 水平与新的炎症性脑损伤的临床表现更为严重相关，而这些患者的疾病进程更好。IL-6 干扰突触可塑性机制可能会损害 RR-MS 患者补偿新脑损伤临床表现的能力。
