The role of inflammatory mediators in epilepsy: Focus on developmental and epileptic encephalopathies and therapeutic implications

•Uncontrolled epileptic activity leads to cognitive, motor and behavior impairment.•Seizures can activate inflammatory pathways that contribute to their persistence.•Innate immunity involvement is evidenced in animal models and epileptic patients.•The treatment of West Syndrome is a paradigm for other epileptic encephalopathies.•Studies should target inflammatory pathways to tailor novel anti-epileptic drugs. In recent years, there has been an increasing interest in the potential involvement of neuroinflammation in the pathogenesis of epilepsy. Specifically, the role of innate immunity (that includes cytokines and chemokines) has been extensively investigated either in animal models of epilepsy and in clinical settings. Developmental and epileptic encephalopathies (DEE) are a heterogeneous group of epileptic disorders, in which uncontrolled epileptic activity results in cognitive, motor and behavioral impairment. By definition, epilepsy in DEE is poorly controlled by common antiepileptic drugs but may respond to alternative treatments, including steroids and immunomodulatory drugs. In this review, we will focus on how cytokines and chemokines play a role in the pathogenesis of DEE and why expanding our knowledge about the role of neuroinflammation in DEE may be crucial to develop new and effective targeted therapeutic strategies to prevent seizure recurrence and developmental regression.