title: Chronic valproate or levetiracetam treatment does not influence cytokine levels in humans.
abstract: OBJECTIVE
  There is growing evidence that complex interactions between seizures and the immune system shape the course of epilepsy. However, systematic analyses of the effects of antiepileptic drugs (AED) on the immune system in humans are rare. We performed a prospective study on the influence of the widely used AED valproate and levetiracetam on interictal immunological parameters.
  
  
  METHODS
  36 patients were prospectively included. 15 were started on valproate (5 female (33%), age 54±27 years, 12 (80%) on monotherapy), 21 on levetiracetam (10 female (48%), age 45±19 years, 17 (81%) on monotherapy). Before treatment and after 3 months, we performed a differential blood count and analyzed the distribution of CD3(+)CD4(+)-, CD3(+)CD8(+)- and CD4(+)CD25(+)-leukocyte subsets using flow cytometry. In addition, we determined the concentrations of IL-1β, IL-6, TNF-α and MCP-1 in the peripheral blood using ELISAs.
  
  
  RESULTS
  Valproate intake resulted in a significant decrease of the total white blood count (6.96±1.23/nl vs. 6.13±1.57/nl, p=0.026) and of absolute count and percentage of neutrophils (4.60±1.05/nl vs. 3.69±1.30/nl, p=0.01; 65.4±7.9% vs. 59.5±11.5%, p=0.01, respectively). The percentage of CD3(+)CD4(+)-lymphocytes dropped significantly (50.4±10.9% vs. 45.3±12.3%, p=0.002). Levetiracetam treatment resulted in a decrease of the percentage of CD4(+)CD25(+)-lymphocytes (26.1±8.0% vs. 21.5±9.2%, p=0.01) but did not significantly alter absolute counts. Neither valproate nor levetiracetam were associated with significant changes in cytokines.
  
  
  CONCLUSIONS
  Valproate intake results in profound changes of white blood cell count and subset distribution. Cytokine levels were not influenced by valproate or levetiracetam.
authors.affiliation: Epilepsy Center Hessen, Department of Neurology, Philipps-University Marburg, Baldingerstr. 1, 35043 Marburg, Germany; University Hospital Munich, Ludwig-Maximilian-University, Marchioninistr. 15, 81377 Munich, Germany. Electronic address: sabina.guenther@med.uni-muenchen.de.
authors.forename: Sabina
authors.initials: S
authors.lastname: Guenther
authors.affiliation: Epilepsy Center Hessen, Department of Neurology, Philipps-University Marburg, Baldingerstr. 1, 35043 Marburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bauer
authors.affiliation: Epilepsy Center Hessen, Department of Neurology, Philipps-University Marburg, Baldingerstr. 1, 35043 Marburg, Germany; Epilepsy Center, Department of Neurology, University of Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Hagge
authors.affiliation: Epilepsy Center Hessen, Department of Neurology, Philipps-University Marburg, Baldingerstr. 1, 35043 Marburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Knake
authors.affiliation: Epilepsy Center, Department of Neurology, University of Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: David G
authors.initials: DG
authors.lastname: Olmes
authors.affiliation: Epilepsy Center Hessen, Department of Neurology, Philipps-University Marburg, Baldingerstr. 1, 35043 Marburg, Germany.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Tackenberg
authors.affiliation: Epilepsy Center Hessen, Department of Neurology, Philipps-University Marburg, Baldingerstr. 1, 35043 Marburg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Rosenow
authors.affiliation: Epilepsy Center Hessen, Department of Neurology, Philipps-University Marburg, Baldingerstr. 1, 35043 Marburg, Germany; Epilepsy Center, Department of Neurology, University of Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Hajo M
authors.initials: HM
authors.lastname: Hamer
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D001774:Blood Chemical Analysis; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D004827:Epilepsy / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007958:Leukocyte Count; D000077287:Levetiracetam; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D016207:Cytokines; D000077287:Levetiracetam; D014635:Valproic Acid; D010889:Piracetam
keywords: Cytokines; Epilepsy; Immune system; Levetiracetam; Lymphocytes; Valproate