Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Advanced Innovation Center for Human Brain Protection, China National Clinical Research Center for Neurological Diseases, Beijing, China.
Biomed Res Int. 2020 Oct 1;2020:3812671. doi: 10.1155/2020/3812671. eCollection 2020.
The aim of this study was to examine the cerebrospinal fluid (CSF) concentrations of proinflammatory and anti-inflammatory cytokines in neurosyphilis (NS), analyze the differences between asymptomatic NS (ANS) and symptomatic NS (SNS), and explore the diagnostic value of these cytokines. We enrolled 45 patients with a diagnosis of NS, including 18 patients with ANS and 27 patients with SNS, whose cerebrospinal fluid (CSF) samples were collected before penicillin therapy. Twelve patients with syphilis but non-NS (NNS) were also included. We measured the CSF levels of interleukin- (IL-) 1, IL-4, IL-6, IL-10, IL-17A, IL-21, and tumor necrosis factor- (TNF-) ; the CSF levels of the microglial activation marker soluble triggering receptor expressed on myeloid cells 2 (sTREM2); and the CSF levels of the neuronal injury marker neurofilament light proteins (NFL) using the human cytokine multiplex assay or ELISA. Of the measured cytokines in the CSF, only IL-10 levels were significantly increased in NS patients compared to NNS patients ( < 0.001). In a subgroup analysis, the CSF levels of IL-10 were significantly elevated in SNS patients compared to ANS and NNS patients ( = 0.024 and < 0.001, respectively). The CSF IL-10 levels had a significant correlation with the markers of microglial activation and neuronal injury, and they also correlated with CSF rapid plasma reagin (RPR) titer, CSF white blood cell (WBC) count, and CSF protein concentration. The areas under the ROC curve (AUC) of CSF IL-10 in the diagnosis of NS and ANS were 0.920 and 0.891, respectively. The corresponding sensitivities/specificities were 86.7%/91.7% and 83.3%/91.7%, respectively. Therefore, the excessive production of IL-10 might facilitate bacterial persistent infection, play an important role in the pathogenesis of NS, and associate with the progression of the disease. CSF IL-10 concentration had a useful value in the diagnosis of NS, especially in ANS.
本研究旨在检测神经梅毒（NS）患者脑脊液（CSF）中促炎和抗炎细胞因子的浓度，分析无症状 NS（ANS）和有症状 NS（SNS）之间的差异，并探讨这些细胞因子的诊断价值。我们纳入了 45 例 NS 患者，其中 18 例为 ANS，27 例为 SNS，所有患者在接受青霉素治疗前均采集了 CSF 样本。同时还纳入了 12 例梅毒而非 NS（NNS）患者作为对照。我们采用人细胞因子多重分析或 ELISA 法检测 CSF 中白细胞介素-（IL-）1、IL-4、IL-6、IL-10、IL-17A、IL-21 和肿瘤坏死因子-（TNF-）；微胶质细胞激活标志物可溶性髓系细胞触发受体 2（sTREM2）；神经元损伤标志物神经丝轻蛋白（NFL）的 CSF 水平。与 NNS 患者相比，NS 患者的 CSF 中仅 IL-10 水平显著升高（<0.001）。在亚组分析中，SNS 患者的 CSF 中 IL-10 水平显著高于 ANS 和 NNS 患者（=0.024 和<0.001）。CSF IL-10 水平与微胶质细胞激活和神经元损伤标志物均呈显著相关，且与 CSF 快速血浆反应素（RPR）滴度、CSF 白细胞（WBC）计数和 CSF 蛋白浓度均呈显著相关。CSF IL-10 对 NS 和 ANS 的诊断的 ROC 曲线下面积（AUC）分别为 0.920 和 0.891，相应的敏感度/特异性分别为 86.7%/91.7%和 83.3%/91.7%。因此，IL-10 的过度产生可能有助于细菌持续感染，在 NS 的发病机制中发挥重要作用，并与疾病的进展相关。CSF IL-10 浓度对 NS 的诊断具有一定的价值，尤其是在 ANS 中。
