Fominykh Vera, Vorobyeva Anna, Onufriev Mikhail V, Brylev Lev, Zakharova Maria N, Gulyaeva Natalia V
Institute of Higher Nervous Activity and Neurophysiology Russian Academy of Sciences, Department of Functional Biochemistry of the Nervous System, Moscow, Russia.
Bujanov Moscow City Clinical Hospital, Moscow, Russia.
J Clin Neurol. 2018 Jul;14(3):327-332. doi: 10.3988/jcn.2018.14.3.327. Epub 2018 May 31.
A few groups have suggested that activated cytokines and nitrosative stress are closely involved in the pathogenesis of different demyelinating disorders induced by the neuroinflammatory destruction of neurons. The purpose of this study was to elucidate the associations of cytokines and S-nitrosothiols (RSNO) with the severity of neurodegeneration during relapse in demyelinating disorders of the central nervous system.
We measured levels of interleukin-6 (IL-6), erythropoietin, RSNO, and phosphorylated neurofilament heavy chain (pNfh) in cerebrospinal fluid (CSF) samples obtained from patients with different demyelinating disorders: multiple sclerosis (MS, n=52), acute disseminated encephalomyelitis (ADEM, n=9), and neuromyelitis optica spectrum disorders (NMOSD) with aquaporin-4 immunoglobulin G (AQP4-IgG, n=12). We compared these levels with those measured in a control group (n=24).
We found that IL-6 in CSF was elevated in NMOSD with AQP4-IgG and ADEM patients as well as in MS patients after the destruction of soluble IL-6. Erythropoietin levels were lower in MS, while RSNO levels were higher in NMOSD with AQP4-IgG and MS patients than in the control group. CSF pNfh levels were elevated in MS and ADEM patients.
These results confirm that IL-6 is activated in different demyelinating disorders, with this elevation being more prominent in the CSF of NMOSD with AQP4-IgG and ADEM patients. Moreover, S-nitrosylation is activated in demyelinating disorders with spinal-cord injury and neurodegeneration in these patients. However, we found no correlation between these biochemical markers, and so we could not confirm whether IL-6-mediated nitric oxide production is involved in spinal-cord lesions.
一些研究小组表明，活化的细胞因子和亚硝化应激与神经元神经炎性破坏所引发的不同脱髓鞘疾病的发病机制密切相关。本研究的目的是阐明细胞因子和S-亚硝基硫醇（RSNO）与中枢神经系统脱髓鞘疾病复发期间神经退行性变严重程度之间的关联。
我们检测了从患有不同脱髓鞘疾病的患者获取的脑脊液（CSF）样本中白细胞介素-6（IL-6）、促红细胞生成素、RSNO和磷酸化神经丝重链（pNfh）的水平，这些患者包括：多发性硬化症（MS，n = 52）、急性播散性脑脊髓炎（ADEM，n = 9）以及伴有水通道蛋白4免疫球蛋白G（AQP4-IgG，n = 12）的视神经脊髓炎谱系障碍（NMOSD）。我们将这些水平与在对照组（n = 24）中测得的水平进行了比较。
我们发现，伴有AQP4-IgG的NMOSD患者、ADEM患者以及可溶性IL-6破坏后的MS患者脑脊液中的IL-6水平升高。MS患者的促红细胞生成素水平较低，而伴有AQP4-IgG的NMOSD患者和MS患者的RSNO水平高于对照组。MS患者和ADEM患者脑脊液中的pNfh水平升高。
这些结果证实，IL-6在不同的脱髓鞘疾病中被激活，在伴有AQP4-IgG的NMOSD患者和ADEM患者的脑脊液中这种升高更为显著。此外，S-亚硝基化在伴有脊髓损伤和神经退行性变的脱髓鞘疾病患者中被激活。然而，我们发现这些生化标志物之间没有相关性，因此无法证实IL-6介导的一氧化氮产生是否参与脊髓损伤。
