title: Targeting inflammation as a therapeutic strategy for drug-resistant epilepsies: an update of new immune-modulating approaches.
abstract: An increasing body of literature data suggests that inflammation, and in particular neuroinflammation, is involved in the pathophysiology of particular forms of epilepsy and convulsive disorders. Animal models have been used to identify inflammatory triggers in epileptogenesis and inflammation has recently been shown to enhance seizures. For example, pharmacological blockade of the IL-1beta/IL-1 receptor type 1 axis during epileptogenesis has been demonstrated to provide neuroprotection in temporal lobe epilepsy. Furthermore, experimental models have suggested that neural damage and the onset of spontaneous recurrent seizures are modulated via complex interactions between innate and adaptive immunity. However, it has also been suggested that inflammation can occur as a result of epilepsy, since animal models have also shown that seizure activity can induce neuroinflammation, and that recurrent seizures maintain chronic inflammation, thereby perpetuating seizures. On the basis of these observations, it has been suggested that immune-mediated therapeutic strategies may be beneficial for treating some drug resistant epilepsies with an underlying demonstrable inflammatory process. Although the potential mechanisms of immunotherapeutic strategies in drug-resistant seizures have been extensively discussed, evidence on the efficacy of such therapy is limited. However, recent research efforts have been directed toward utilizing the potential therapeutic benefits of anti-inflammatory agents in neurological disease and these are now considered prime candidates in the ongoing search for novel anti-epileptic drugs. The objective of our review is to highlight the immunological features of the pathogenesis of seizures and to analyze possible immunotherapeutic approaches for drug resistant epilepsies that can alter the immune-mediated pathogenesis.
authors.affiliation: Department of Paediatrics and Pediatric Acute and Emergency Unit; Policlinico-Vittorio Emanuele University Hospital; University of Catania; Catania, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Vitaliti
authors.affiliation: Department of Paediatrics and Pediatric Acute and Emergency Unit; Policlinico-Vittorio Emanuele University Hospital; University of Catania; Catania, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Pavone
authors.affiliation: University London College Medical School; University of London; London, UK.
authors.forename: Fahad
authors.initials: F
authors.lastname: Mahmood
authors.affiliation: Department of Infectious Diseases; Garibaldi Nesima Hospital; University of Catania; Catania, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nunnari
authors.affiliation: Department of Paediatrics and Pediatric Acute and Emergency Unit; Policlinico-Vittorio Emanuele University Hospital; University of Catania; Catania, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Falsaperla
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004351:Drug Resistance; D004827:Epilepsy / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D020078:Neurogenic Inflammation / Q000188:drug therapy*; D015213:Neuroimmunomodulation
chemical_list: D000893:Anti-Inflammatory Agents
keywords: childhood; drug resistent epilepsy; immunophlogosis; immunotherapeutic approaches