Interleukin 18 (IL-18) and its binding protein (IL-18BP) are increased in patients with epilepsy suggesting low-grade systemic inflammation

Purpose: Proinflammatory cytokines seems to play a role in epileptogenesis independent of the underlying cause. The purpose of this study was to assess if IL-18 and its binding protein IL-18BP are related to epilepsy and could act as a predictive biomarker for epileptogenesis. Methods: In this cross-sectional study, circulating levels of IL-18 and IL-18BP were analysed in 119 epilepsy patients, and 80 healthy controls. Participants completed a questionnaire regarding epilepsy, use of drug(-s) and comorbidity. Results: Epilepsy patients had significantly higher serum levels of IL-18 (p= 0.003) and IL-18BP (p= 0.009) than healthy controls. The groups differed in sex, age and weight, however none of those variables were significantly correlated with IL-18 and IL-18BP in patients or controls. Weight was considered an important confounder in our study. Subgroup investigations revealed that in participants with BMI under 30 kg/m(2), serum IL18 (p= 0.032) and IL-18BP (p= 0.029) remained significantly higher in patients than controls. Further analyses showed significantly higher concentration of IL-18 among participants using carbamazepine (CBZ) (p= 0.016) or lamotrigine (LTG) (p= 0.024), but not in those using levetiracetam (LEV) (p= 0.102) compared to controls. No associations were found between serum levels of IL-18 and IL-18BP and epilepsy duration, seizures type, or presence of seizures in the last six months. Conclusion: The study shows an elevation of IL-18 and IL-18BP serum levels in epilepsy patients. This result indicates the presence of a low-grade systemic inflammation involving IL-18 in epilepsy. Further investigations should explore the character and clinical impact of IL-18 as well its possible role as a biomarker for epilepsy.