Concentration of Il-1ß, Il-2, Il-6, TNFα in the blood serum in children with generalized epilepsy treated by valproate.

BACKGROUND: The aim of the study was the comparison of concentrations of IL-1ß, IL-2, IL-6 and TNFα before and after valproate (VPA) treatment in blood serum in patients with generalized seizures diagnosed and treated in the Department of Developmental Neurology, Poznan University of Medical Sciences from January 2006 to May 2007. METHODS: The analysis was conducted in a group of 21 patients with well controlled, generalized seizures (mean age 7.7±4.7 years) before and after 4-6 months of VPA therapy. Quantitative determination IL-1ß, IL-2, IL-6 and TNFα were performed with method of enzyme-linked immunosorbent assay (ELISA). The serum drug concentration was determined with the use of fluorescence-polarization-immunoassay system (FPIA). RESULTS: The concentration of IL-6 in blood serum of patients decreased significantly (p<0.001) after 4-6 months of VPA therapy, but concentration of IL-1ß (p=0.732), IL-2 (p=0.865), TNFα (p=0.079) did not change significantly. The serum concentration of VPA in all of patients was in therapeutic range (mean 77.53±19.71µg/ml). CONCLUSIONS: The serum level of pro-inflammatory IL-6 in patients with generalized epilepsy decreased in statistically significant way during VPA therapy, so the anti-inflammatory properties of VPA are also important for the effective control of seizure. Due to the incompatibility of reports on the influence of VPA on cytokine system in patients with generalized epilepsy, this problem needs more investigations, especially in the group of children.

Cytokines, epilepsy and epileptic drugs--is there a mutual influence?

In recent years, the functional disturbances of the immune system, both humoral and cell-mediated immunity, have been detected more often among persons with epilepsy than in general population. A number of irregularities in cytokine production have been found in epileptic patients. It shows that epileptic seizures stimulate, per se, synthesis of pro-inflammatory and pro-convulsive cytokines. Some antiepileptic drugs (AEDs) influence the production of cytokines, too. The influence of AEDs on cytokine concentrations in blood has been observed, e.g. during carbamazepine (CBZ) or valproic acid (VPA) therapy. This article is a review of the literature which focuses on the connections between epilepsy and the cytokine system as well as on the influence of AEDs on the cell-mediated and humoral response in epileptic patients. Correlation of immunological irregularities in patients with the type, dosage, and serum level of AEDs will allow for early detection of undesirable treatment consequences in epilepsy. Elucidation of connections between cytokine system, epileptogenesis and effectiveness of AED therapy requires a better planned research on larger groups of patients with epilepsy.