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

Monika Mochol; Erik Taubøll; Pål Aukrust; Thor Ueland; Ole A Andreassen; Sigrid Svalheim

doi:10.1016/j.seizure.2020.05.018

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

Seizure. 2020 Aug:80:221-225. doi: 10.1016/j.seizure.2020.05.018. Epub 2020 May 29.

Authors

Monika Mochol¹, Erik Taubøll², Pål Aukrust³, Thor Ueland⁴, Ole A Andreassen⁵, Sigrid Svalheim⁶

Affiliations

¹ Department of Neurology, Østfold Hospital Trust, Norway; ERGO - Epilepsy Research Group of Oslo, Department of Neurology, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Norway. Electronic address: monikamochol@hotmail.com.
² ERGO - Epilepsy Research Group of Oslo, Department of Neurology, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Norway.
³ Institute of Clinical Medicine, University of Oslo, Norway; Department of Immunology and Infectious Disease, Oslo University Hospital, Norway.
⁴ Institute of Clinical Medicine, University of Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Norway; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Norway.
⁵ NORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Norway.
⁶ ERGO - Epilepsy Research Group of Oslo, Department of Neurology, Oslo University Hospital, Norway.

PMID: 32659652
DOI: 10.1016/j.seizure.2020.05.018

Abstract

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/m², serum IL-18 (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.

Keywords: Antiseizure medication; Epilepsy; Epileptogenesis; Interleukin-18; Interleukin-18 binding protein; Neuroinflammation.

MeSH terms

Cross-Sectional Studies
Epilepsy* / drug therapy
Humans
Inflammation
Intercellular Signaling Peptides and Proteins / blood*
Interleukin-18* / blood

Substances

IL18 protein, human
Intercellular Signaling Peptides and Proteins
Interleukin-18
interleukin-18 binding protein