IL-1β and HMGB1 in Epileptogenesis: Recent Advances and Clinical Translation

Epilepsy is one of the most prevalent and disabling neurological disorders, affecting approximately one percent of the population. Due to the complex pathophysiology underlying drug-resistant epilepsy, nearly one-third of patients with epilepsy do not benefit from current treatments. Neuroinflammation is one of the most well-studied pathways in epileptogenesis, and inflammatory mediators play a crucial role in this process. The IL-1β/IL-1R1/IL-1Ra and HMGB1/TLR4 pathways play significant roles in epileptogenesis in both animal and human studies. Interventional investigations on the IL-1β/IL-1R1/IL-1Ra and HMGB1/TLR4 pathways showed antiseizure effects, suggesting that these pathways could be therapeutic targets for epilepsy. However, related targeted treatments are limited in clinical practice. In this work, we evaluated the advances of the IL-1β/IL-1R1/IL-1Ra and HMGB1/TLR4 pathways in epileptogenesis, as well as clinical trials or interventional investigations of current medications or substances targeting these pathways. To facilitate clinical translation, we highlighted the gap between research advancements and clinical practice and presented several strategies for closing the gap to fulfill the urgent requirements of patients with epilepsy.