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CCL2/MCP-1、白细胞介素-8 和 fractalkine/CXC3CL1:儿童癫痫发生和药物抵抗的潜在生物标志物。

CCL2/MCP-1, interleukin-8, and fractalkine/CXC3CL1: Potential biomarkers of epileptogenesis and pharmacoresistance in childhood epilepsy.

机构信息

Department of Pediatric Neurology, Brno Epilepsy Center, University Hospital, Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Department of Pediatrics, University Hospital, Faculty of Medicine, Masaryk University, Brno, Czech Republic.

出版信息

Eur J Paediatr Neurol. 2023 Sep;46:48-54. doi: 10.1016/j.ejpn.2023.06.001. Epub 2023 Jun 15.

DOI:10.1016/j.ejpn.2023.06.001
PMID:37429062
Abstract

OBJECTIVE

The pathophysiological processes leading to epileptogenesis and pharmacoresistance in epilepsy have been the subject of extensive preclinical and clinical research. The main impact on clinical practice is the development of new targeted therapies for epilepsy. We studied the importance of neuroinflammation in the development of epileptogenesis and pharmacoresistance in childhood epilepsy patients.

METHODS

A cross-sectional study conducted at two epilepsy centers in the Czech Republic compared 22 pharmacoresistant patients and 4 pharmacodependent patients to 9 controls. We analyzed the ProcartaPlex™ 9-Plex immunoassay panel consisting of interleukin (IL)-6, IL-8, IL-10, IL-18, CXCL10/IP-10, monocyte chemoattractant protein 1 (CCL2/MCP-1), B lymphocyte chemoattractant (BLC), tumor necrosis factor-alpha (TNF-α), and chemokine (C-X3-X motif) ligand 1 (fractalkine/CXC3CL1) to determine their alterations in cerebrospinal fluid (CSF) and blood plasma, concurrently.

RESULTS

The analysis of 21 paired CSF and plasma samples in pharmacoresistant patients compared to controls revealed a significant elevation of CCL2/MCP-1 in CSF (p < 0.000512) and plasma (p < 0.00.017). Higher levels of fractalkine/CXC3CL1 were revealed in the plasma of pharmacoresistant patients than in controls (p < 0.0704), and we determined an upward trend in CSF IL-8 levels (p < 0.08). No significant differences in CSF and plasma levels were detected between pharmacodependent patients and controls.

CONCLUSION

Elevated CCL2/MCP-1 in CSF and plasma, elevated levels of fractalkine/CXC3CL1 in CSF, and a trend toward elevated IL-8 in the CSF of patients with pharmacoresistant epilepsy indicate these cytokines as potential biomarkers of epileptogenesis and pharmacoresistance. CCL2/MCP-1was detected in blood plasma; this assessment may be easily achieved in clinical practice without the invasiveness of a spinal tap. However, due to the complexity of neuroinflammation in epilepsy, further studies are warranted to confirm our findings.

摘要

目的

导致癫痫发生和耐药性的病理生理过程一直是广泛的临床前和临床研究的主题。对临床实践的主要影响是为癫痫开发新的靶向治疗方法。我们研究了神经炎症在儿童癫痫患者癫痫发生和耐药性发展中的重要性。

方法

捷克共和国的两个癫痫中心进行了一项横断面研究,将 22 名耐药性患者和 4 名药物依赖性患者与 9 名对照进行比较。我们分析了包含白细胞介素 (IL)-6、IL-8、IL-10、IL-18、CXCL10/IP-10、单核细胞趋化蛋白 1 (CCL2/MCP-1)、B 淋巴细胞趋化因子 (BLC)、肿瘤坏死因子-α (TNF-α)和趋化因子 (C-X3-C 基序)配体 1 ( fractalkine/CXC3CL1) 的 ProcartaPlex™ 9-Plex 免疫分析试剂盒,以同时确定其在脑脊液 (CSF) 和血浆中的变化。

结果

与对照组相比,对 21 对耐药性患者的 CSF 和血浆样本进行分析显示,CSF(p < 0.000512)和血浆(p < 0.00.017)中的 CCL2/MCP-1 显著升高。与对照组相比,耐药性患者的血浆中 fractalkine/CXC3CL1 水平更高(p < 0.0704),并且我们确定 CSF IL-8 水平呈上升趋势(p < 0.08)。药物依赖性患者与对照组之间在 CSF 和血浆水平均无显着差异。

结论

耐药性癫痫患者 CSF 和血浆中 CCL2/MCP-1 升高,CSF 中 fractalkine/CXC3CL1 水平升高,CSF 中 IL-8 呈上升趋势,表明这些细胞因子可能是癫痫发生和耐药性的潜在生物标志物。CCL2/MCP-1 在血浆中被检测到;这种评估可以在没有脊髓穿刺的侵入性的情况下在临床实践中轻松完成。然而,由于癫痫中的神经炎症复杂,需要进一步的研究来证实我们的发现。

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