Neurology, Campus Bio-Medico University, Rome, Italy.
Epilepsy Res. 2013 Dec;107(3):244-52. doi: 10.1016/j.eplepsyres.2013.09.010. Epub 2013 Sep 28.
Inflammation has been shown to play a key role in epilepsy, and may also affect both the iron status and metabolism. Consequently, a relationship between iron metabolism and neuronal excitability and seizures could be expected.
We aimed at characterizing in 37 adult patients affected by focal epilepsy during the interictal period serum inflammatory cytokines, such as interleukin 6 (IL-6), IL-6 soluble receptor (IL6-sR), interleukin 1 (IL-1), IL-1 receptor-antagonist (IL-1RA), tumor necrosis factor-α (TNF-α), and markers of iron status and metabolism: hemoglobin concentration (Hgb), mean corpuscular volume (MCV), hematocrit (Hct) red blood cell (RBC) count, serum iron and copper concentrations, ceruloplasmin (iCp), the ceruloplasmin enzymatic activity (eCp), the specific ceruloplasmin activity (eCp/iCp), total ferroxidase activity, transferrin (Tf), serum ferritin (SF), Tf saturation (Sat-Tf), and ratio of ceruloplasmin to transferrin (Cp/Tf). We investigated the correlations between these biological markers as well their relationship with patients' clinical features. A group of 43 healthy subjects had the same serologic measurements to serve as controls.
Our findings showed in the group of patients with epilepsy an increase of IL-6 (p=0.026) and a decrease of TNF-α (p=0.002) with respect to healthy subjects. For the first time, we also detected significant changes in iron metabolism as an increase of Cp/Tf (p=0.011) and a decrease of Tf (p=0.031), possibly driven by cytokine modifications and consistent with inflammation as acute phase and antioxidant activity markers. Accordingly, TNF-α positively correlated with Tf (p=0.005). Finally, a significant positive correlation between seizures frequency and eCp (p=0.046) and inversely with Hgb (p=0.038) and Hct (p=0.041), and an inverse correlation between TNF-α and the duration of epilepsy (p=0.021) was detected.
Our findings demonstrate a relevant relationship between epilepsy and systemic inflammation, with a consistent link between seizures, inflammatory cytokines (IL-6 and TNF-α) and iron regulation and metabolism, as acute phase and antioxidant markers.
炎症在癫痫中起着关键作用，也可能影响铁状态和新陈代谢。因此，可以预期铁代谢与神经元兴奋性和癫痫发作之间存在关系。
我们旨在对 37 名患有局灶性癫痫的成年患者在发作间期进行特征描述，其血清炎症细胞因子，如白细胞介素 6（IL-6）、白细胞介素 6 可溶性受体（IL6-sR）、白细胞介素 1（IL-1）、白细胞介素 1 受体拮抗剂（IL-1RA）、肿瘤坏死因子-α（TNF-α），以及铁状态和代谢标志物：血红蛋白浓度（Hgb）、平均红细胞体积（MCV）、血细胞比容（Hct）、红细胞计数、血清铁和铜浓度、铜蓝蛋白（iCp）、铜蓝蛋白酶活性（eCp）、特异性铜蓝蛋白活性（eCp/iCp）、总铁氧化酶活性、转铁蛋白（Tf）、血清铁蛋白（SF）、Tf 饱和度（Sat-Tf）和铜蓝蛋白与转铁蛋白的比值（Cp/Tf）。我们研究了这些生物标志物之间的相关性及其与患者临床特征的关系。一组 43 名健康受试者进行了相同的血清学测量，作为对照。
我们的研究结果显示，在癫痫患者组中，IL-6 增加（p=0.026），TNF-α 降低（p=0.002），与健康对照组相比。我们首次还检测到铁代谢的显著变化，如 Cp/Tf 增加（p=0.011）和 Tf 减少（p=0.031），这可能是由细胞因子的改变驱动的，与炎症作为急性期和抗氧化活性标志物一致。相应地，TNF-α与 Tf 呈正相关（p=0.005）。最后，检测到癫痫发作频率与 eCp 呈显著正相关（p=0.046），与 Hgb 呈负相关（p=0.038），与 Hct 呈负相关（p=0.041），TNF-α与癫痫持续时间呈负相关（p=0.021）。
我们的研究结果表明癫痫与全身炎症之间存在密切关系，癫痫发作、炎症细胞因子（IL-6 和 TNF-α）与铁调节和代谢之间存在一致性，作为急性期和抗氧化标志物。
