Epilepsy Center Hessen, Department of Neurology, Philipps-University Marburg, Baldingerstr. 1, 35043 Marburg, Germany.
Seizure. 2013 Jul;22(6):462-6. doi: 10.1016/j.seizure.2013.03.006. Epub 2013 Apr 29.
To further elucidate possible immune-modulatory effects of valproate (VPA) or levetiracetam (LEV), we investigated their influence on apoptosis and cytotoxic function of CD8+ T lymphocytes in humans.
In 15 healthy subjects (9 female (60%), 35.7±12.1 years), apoptosis and cytotoxic function of CD8+ T lymphocytes were measured using flow cytometry following in vitro exposure to LEV (5 mg/L and 50 mg/L) and VPA (10mg/L and 100 mg/L). Apoptosis rates were determined after incubation with LEV or VPA for 1 h or 24 h. Cytotoxic function was assessed following 2h stimulation with mixed virus peptides, using perforin release, CD107a/b expression and proliferation. The presence of synaptic vesicle protein 2A (SV2A) was investigated in human CD8+ T lymphocytes by flow cytometry analysis, Western blot and real time polymerase chain reaction (rtPCR).
High concentration of LEV decreased perforin release of CD8+ T lymphocytes (LEV 50 mg/L vs. CEF only: 21.4% (interquartile range (IQR) 16.5-35.9%) vs. 16.6% (IQR 12-24.9%), p=0.002). LEV had no influence on apoptosis and proliferation (p>0.05). VPA (100 mg/L) slowed apoptosis of CD8() T lymphocytes after 24h (VPA 100mg/L vs. control: 7.3% (IQR 5.4-9.5%) vs. 11.3% (IQR 8.2-15.1%), p<0.001), but had no effects on perforin release (p>0.05). SV2A protein was detected in CD8+ T lymphocytes.
LEV decreased degranulation of CD8+ T lymphocytes which may contribute to the increased incidence of upper respiratory tract infections in LEV treated patients. Inhibition of SV2A may be responsible for this effect.
为了进一步阐明丙戊酸（VPA）或左乙拉西坦（LEV）可能具有的免疫调节作用，我们研究了它们对人类 CD8+T 淋巴细胞凋亡和细胞毒性功能的影响。
在 15 名健康受试者（9 名女性（60%），35.7±12.1 岁）中，通过流式细胞术检测体外暴露于 LEV（5mg/L 和 50mg/L）和 VPA（10mg/L 和 100mg/L）后 CD8+T 淋巴细胞的凋亡和细胞毒性功能。孵育 1 小时或 24 小时后测定凋亡率。用穿孔素释放、CD107a/b 表达和增殖评估 2 小时混合病毒肽刺激后的细胞毒性功能。通过流式细胞术分析、Western blot 和实时聚合酶链反应（rtPCR）检测人 CD8+T 淋巴细胞中突触小泡蛋白 2A（SV2A）的存在。
高浓度 LEV 降低 CD8+T 淋巴细胞的穿孔素释放（LEV 50mg/L 与 CEF 相比：21.4%（IQR 16.5-35.9%）与 16.6%（IQR 12-24.9%），p=0.002）。LEV 对凋亡和增殖无影响（p>0.05）。VPA（100mg/L）在 24 小时后减缓 CD8+T 淋巴细胞的凋亡（VPA 100mg/L 与对照相比：7.3%（IQR 5.4-9.5%）与 11.3%（IQR 8.2-15.1%），p<0.001），但对穿孔素释放无影响（p>0.05）。在 CD8+T 淋巴细胞中检测到 SV2A 蛋白。
LEV 降低 CD8+T 淋巴细胞脱颗粒，这可能导致 LEV 治疗患者上呼吸道感染发生率增加。SV2A 的抑制可能是造成这种效应的原因。
