P.1.009 - The role of neuroinflammation in pathogenesis of epilepsy and the possibility of neuroimmunomodulation

Abstract

Introduction Currently, there is ample experimental and clinical evidence of the inflammatory of epileptogenesis and the dysregulation of neurotrophins [1,2]. The activation of microglia and astrogliosis contribute to the сhronic inflammatory process in epilepsy, which damages neurons. The inflammation in the central nervous system is based on damage to the blood-brain barrier (BBB) [3]. Cytokines play a central role in this process, mainly because they are natural pro- and anticonvulsants. The influence of cytokines on the neuronal transmission of mediators contributes to the development of hyperexcitability of the neurons [4]. The cell-mediated immune activation and the process of inflammation induce the dysregulation of a brain-derived neurotrophic factor (BDNF) resulting in a decrease in the hippocampal neurogenesis and neurodegeneration associated with epileptogenesis [5]. Aim To investigate the status and concentration of BDNF in blood plasma of patients with epilepsy (PE) before and after treatment with recombinant human interleukin IL-2 (rIL-2). Materials and method The concentration of cytokines IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α, RAIL-1, sIL-2R and BDNF were analyzed in blood and cerebrospinal fluid (CSF) samples of 160 patients with epilepsy and 31 healthy donors (HD) using enzyme-linked immunosorbent assay (ELISA). The rIL-2-medicament (Roncoleukin ®) was used as adjuvant therapy to basic treatment with antiepileptic drugs in 80 PE. The Roncoleukin ® was injected subcutaneously in a solution of 1 ml at 1.0 mg (1000000 ME rIL-2), number 3. Statistical analysis was performed using Student's t-test and Mann-Whitney U-test. Differences were considered statistically significant at p Results The study showed a significant disbalance of cytokines in PE: increased levels of pro-inflammatory cytokines [IL-1β (316,5±4,0 pg/ml), IL-8 (157,1±99,4 pg/ml) and TNF-α (14±3 pg/ml)], a decrease in the concentration of the receptor antagonist IL-1 (RAIL-1) (38 pg/ml), and significantly reduced content of BDNF (4448,9±780,4 pg/ml). Levels of cytokines IL-1β, IL-2, IL-6 and RAIL-1 did not change significantly after the short course of the complex therapy with rIL-2 medicament; however, the concentration of IL-8 was significantly reduced after treatment with rIL-2 medicament [28,7±15,56 pg/ml and 6,3±1,4 pg/ml, respectively (p Conclusions Our results support the cytokine theory of epilepsy. The data showed a decrease in concentration of proinflammatory IL-8 and an increase in the content of BDNF in PE as a result of rIL-2 medicament. The increase of pro-inflammatory cytokines in CSF in PE indicates a damage of BBB and the existence of a systemic inflammatory process. The absence of RAIL-1 indicates a reduction in the protective factors of inflammation in blood and CSF. Changes in the expression of BDNF in PE after the treatment of rIL-2h should be considered from the standpoint of neuroplasticity as a predictor of therapeutic response in PE. These results could be used to optimize the treatment of patients with epilepsy due to modulation of the inflammatory process and increase the production of neurotrophic factors required for the neuroplasticity and neurogenesis processes.