Wang Ye, Wang Desheng, Guo Dawen
Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, Peoples' Republic of China.
Department of Clinical Laboratory, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, Peoples' Republic of China.
J Transl Med. 2015 Dec 1;13:378. doi: 10.1186/s12967-015-0742-3.
Many aspects on the correlation between epilepsy and cytokine levels were unclear. This study aims to investigate the correlations between cytokine levels and severe epilepsy.
Totally 1218 epileptic patients were grouped by types of epilepsy: TLE (temporal lobe epilepsy, n = 409), XLE (extra-temporal lobe epilepsy, n = 290) and IGE (idiopathic generalized epilepsy, n = 519). Two hundred healthy volunteers were as controls. Clinical findings and levels of 14 serum and CSF cytokines and 6 STAT members were collected, measured and analyzed.
Analysis showed no differences in interictal cytokine levels among patients from TLE, XLE and IGE groups. Interictal serum levels of IL-1b, IL-1Ra, IL-6, IL-8, IFNγ, IFNλ3 and IL-17a were associated with seizure severity of epileptic patients, measured by seizure frequency, VA score or NHS3. Multivariate regression analysis indicated that interictal concentrations of serum IL-6, IFNγ, IL-17a, IFNλ3, and CSF IL-6, IL-17a, IFNλ3 were significant biomarkers for patients with severe epilepsy. mRNA levels of IL-6, IFNγ, IL-17a, and IFNλ3 were elevated in different types of epilepsy. Activation of all STATs was elevated in epilepsy, and STAT3 was activated 9-fold in average, which was the highest among all STATs.
Interictal serum IL-6, IFNγ, IL-17a, IFNλ3, and CSF IL-6, IL-17a, IFNλ3 could be used as potential biomarkers for severe epilepsy. Activation of STATs, especially STAT3, was important in epilepsy. Our findings pointed out crucial roles of cytokine levels in epilepsy.
癫痫与细胞因子水平之间相关性的许多方面尚不清楚。本研究旨在探讨细胞因子水平与重度癫痫之间的相关性。
1218例癫痫患者按癫痫类型分组:颞叶癫痫(TLE,n = 409)、颞外叶癫痫(XLE,n = 290)和特发性全身性癫痫(IGE,n = 519)。200名健康志愿者作为对照。收集、测量并分析临床资料以及14种血清和脑脊液细胞因子水平及6种信号转导和转录激活因子(STAT)成员水平。
分析显示,TLE、XLE和IGE组患者发作间期细胞因子水平无差异。发作间期血清白细胞介素-1β(IL-1β)、白细胞介素-1受体拮抗剂(IL-1Ra)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、干扰素γ(IFNγ)、干扰素λ3(IFNλ3)和白细胞介素-17a(IL-17a)水平与癫痫患者的发作严重程度相关,发作严重程度通过发作频率、视觉模拟评分(VA评分)或神经功能缺损评分3(NHS3)来衡量。多因素回归分析表明,发作间期血清IL-6、IFNγ、IL-17a、IFNλ3以及脑脊液IL-6、IL-17a、IFNλ3浓度是重度癫痫患者的重要生物标志物。不同类型癫痫中IL-6、IFNγ、IL-17a和IFNλ3的信使核糖核酸(mRNA)水平均升高。癫痫中所有STATs的激活均升高,STAT3平均激活9倍,在所有STATs中激活程度最高。
发作间期血清IL-6、IFNγ、IL-17a、IFNλ3以及脑脊液IL-6、IL-17a、IFNλ3可作为重度癫痫的潜在生物标志物。STATs的激活,尤其是STAT3的激活在癫痫中起重要作用。我们的研究结果指出了细胞因子水平在癫痫中的关键作用。