title: Levetiracetam but not valproate inhibits function of CD8+ T lymphocytes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Epilepsy Center Hessen, Department of Neurology, Philipps-University Marburg, Baldingerstr. 1, 35043 Marburg, Germany.
authors: Gang
authors: G
authors: Li
authors: Mareike
authors: M
authors: Nowak
authors: Sebastian
authors: S
authors: Bauer
authors: Kerstin
authors: K
authors: Schlegel
authors: Susanne
authors: S
authors: Stei
authors: Lena
authors: L
authors: Allenhöfer
authors: Anne
authors: A
authors: Waschbisch
authors: Björn
authors: B
authors: Tackenberg
authors: Matthias
authors: M
authors: Höllerhage
authors: Günter U
authors: GU
authors: Höglinger
authors: Sven
authors: S
authors: Wegner
authors: Xin
authors: X
authors: Wang
authors: Wolfgang H
authors: WH
authors: Oertel
authors: Felix
authors: F
authors: Rosenow
authors: Hajo M
authors: HM
authors: Hamer
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D054353:Perforin / Q000378:metabolism; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D018709:Statistics, Nonparametric; D014635:Valproic Acid / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D015703:Antigens, CD; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D054353:Perforin; C076414:SV2A protein, human; D000077287:Levetiracetam; D014635:Valproic Acid; D010889:Piracetam