Neuroinflammation in epilepsy: an analysis of patients' sera and its effect on microglia-like cells

Objective: Characterize neuroinflammatory markers in the sera of patients with epilepsy and assess its influence on the phenotype of healthy control derived microglia-like cells (MDMi) in vitro. Background: One-third of patients with epilepsy do not respond to anticonvulsant medications and continue to have seizures. Traditional investigations have focused on the excitation-inhibition model with ion channels as key players, while the role of peripheral and central neuroinflammation in the pathophysiology remains unclear. Design/Methods: Patients with focal epilepsy were prospectively recruited from an academic epilepsy clinic and completed the beck depression inventory II (BDI-II). Patients were divided into those with or without seizures over the past 6 months (well vs. poorly controlled), and sera were analyzed for inflammatory mediators using a Luminex platform measuring 60 cytokines and chemokines. Nine healthy control derived MDMi were exposed to the serum of 2 poorly controlled and 2 well controlled patients to assess a change in the pattern of expression of cytokines/chemokines. Results: A total of 68 epilepsy patients (45.6% poorly controlled) were recruited; 63% were male with mean age 38.2 ± 12.0 years. Characteristics of the poorly controlled v.s. well controlled group: mean BDI-II (10.4 ± 9.5 v.s. 8.0 ± 8.7), MRI abnormality present (49% v.s 49%), and temporal lobe epilepsy (74% V.S. 62%). A trend for lower interferon-2a and interleukin(IL)-12p70 levels were noted in the poorly controlled group. BDI-II scores across the entire epilepsy cohort positively correlated with IL-1a and IL-10 levels. In the pilot experiment, MDMi exposed to poorly controlled sera revealed significantly higher levels of the chemokine CXCL1 (a neutrophil chemoattractant). Conclusions: Our preliminary findings suggest that there may be differences in circulating mediators of inflammation in patients with poorly controlled seizures as well as an association between increased proinflammatory mediators with increased depressive scores in epilepsy. Study Supported by: UCB provided research funding for portions of the study Disclosure: Dr. Sarkis has nothing to disclose. Dr. Olah has nothing to disclose. Dr. Llewellyn has nothing to disclose. Dr. Buttrick has nothing to disclose. Dr. Ryan has nothing to disclose. Dr. De Jager has received research support from Biogen Idec and Genzyme. Dr. Pennell has nothing to disclose. Dr. Bradshaw has received personal compensation for activities with Eisai as a speaker. Dr. Elyaman has received research support from UCB Inc.