The balance of inhibitory and excitatory cytokines is differently regulated in vivo and in vitro among therapy resistant epilepsy patients
The balance of inhibitory and excitatory cytokines is differently regulated in vivo and in vitro among therapy resistant epilepsy patients
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DOI：
10.1016/j.eplepsyres.2004.04.007
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发表时间：
2004-04-01
影响因子：
2.2
通讯作者：
Peltola, J
中科院分区：
文献类型：
--
作者：
Hulkkonen, J;Koskikallio, E;Peltola, J
目的：过度的神经元活动和癫痫发作直接刺激细胞因子的表达。在这项研究中，我们研究了循环血液和外周血单核细胞（PBMC）中细胞因子的产生，以评估这些细胞因子在难治性癫痫患者中的细胞来源。研究方法：我们比较了10例难治性定位相关癫痫患者和健康志愿者的血浆IL-1 β、IL-1 Ra和IL-6水平。使用EIA在PBMC培养物中研究这些细胞因子的自发和外源刺激产生。此外，使用流式细胞术研究细胞特异性细胞因子的产生。结果如下：在癫痫患者血浆中观察到高度促炎细胞因子谱（高IL-6、低IL-1 Ra和低IL-1 Ra/IL-1 β比值）。在患者和对照受试者的PBMC培养物中，自发和LPS刺激的细胞因子释放是相似的。当用OKT 3刺激细胞时，癫痫患者中的细胞因子应答谱与在循环血液中观察到的谱几乎相反（抗炎）。当用PDBu + A23187刺激时，在患者的细胞培养物中观察到低IL-6。流式细胞术分析显示，患者和对照组中IL-1 β、IL-1 Ra和IL-6阳性单核细胞的百分比相似。结论：具有治疗抗性癫痫的患者显示血浆细胞因子的促炎性特征，而没有任何证据表明PBMC的产生增加。这些结果表明，这些细胞因子最可能的来源是大脑，细胞因子可以发挥神经调节功能。(C)2004 Elsevier B. V.保留所有权利。
Purpose: Excessive neuronal activity and seizures directly stimulate cytokine expression. In this study we investigated cytokine production in circulating blood and peripheral blood mononuclear cells (PBMC) in order to assess the cellular origin of these cytokines in patients with therapy resistant epilepsy. Methods: We compared the levels of plasma IL-1beta, IL-1Ra and IL-6 in 10 patients with therapy resistant localization-related epilepsy and in healthy volunteers. The spontaneous and exogenously stimulated production of these cytokines was studied in PBMC cultures using EIA. Moreover, cell-specific cytokine production was studied using flow cytometry. Results: Highly pro-inflammatory cytokine profile (high IL-6, low IL-1Ra and low IL-1Ra/IL-1beta ratio) was observed in plasma from patients with epilepsy. Spontaneous and LPS stimulated cytokine release was similar in PBMC cultures of patients and control subjects. When cells were stimulated with OKT3 the cytokine response profiles in patients with epilepsy were almost opposite (anti-inflammatory) to the profile which was observed in circulating blood. Low IL-6 was observed in cell cultures of patients when stimulated with PDBu + A23187. Flow cytometric analysis revealed that the percentages of IL-1beta, IL-1Ra and IL-6 positive monocytes were similar in patients and control subjects. Conclusions: Patients with therapy resistant epilepsy display a pro-inflammatory profile of plasma cytokines without any evidence of increased production from PBMC. These results suggest that the most likely origin for these cytokines is the brain, where cytokines can exert neuromodulatory functions. (C) 2004 Elsevier B.V. All rights reserved.