Levetiracetam but not valproate inhibits function of CD8⁺ T lymphocytes

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• 作者：Gang Li ; Mareike Nowak ; Sebastian Bauer ; Kerstin Schlegel ; Susanne Stei ; Lena Allenh?fer ; Anne Waschbisch ; Bj?rn Tackenberg ; Matthias H?llerhage ; G¨¹nter U. H?glinger ; Sven Wegner ; Xin Wang ; Wolfgang H. Oertel ; Felix Rosenow ; Hajo M. Hamer
• 关键词：Levetiracetam ; Valproate ; CD8+ T lymphocytes ; Apoptosis ; SV2A ; Perforin
• 刊名：Seizure
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：22
• 期：6
• 页码：462-466
• 全文大小：502 K

文摘

<h4 class=""h4"">Purposeh4>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.<h4 class=""h4"">Methodsh4>

In 15 healthy subjects (9 female (60 % ), 35.7 ¡À 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 (10 mg/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 2 h 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).<h4 class=""h4"">Resultsh4>

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 24 h (VPA 100 mg/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.<h4 class=""h4"">Conclusionh4>

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.