title: Therapeutic potential of new antiinflammatory drugs.
abstract: Experimental and clinical findings have shown in the past decade that specific proinflammatory mediators and their cognate receptors are upregulated in epileptic brain tissue. In particular, the IL-1 receptor (R)/Toll-like receptor (TLR) signaling pathways are activated in experimental models of seizures and in human epileptic tissue from drug-resistant patients. Pharmacological targeting of these proinflammatory pathways using selective receptor antagonists, or the use of transgenic mice with perturbed cell signaling, demostrated that the activation of IL-1R type 1 and TLR4 by their respective endogenous ligands, i.e., interleukin (IL)-1b and High Mobility Group Box 1, is implicated in the precipitation and recurrence of experimentally induced seizures in rodents. This evidence highlights a new target system for pharmacological intervention to inhibit seizures by interfering with mechanisms involved in their genesis and recurrence.
authors.affiliation: Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Via G. La Masa 19, Milan, Italy. vezzani@marionegri.it
authors.forename: Annamaria
authors.initials: A
authors.lastname: Vezzani
authors.forename: Tamas
authors.initials: T
authors.lastname: Bartfai
authors.forename: Marco
authors.initials: M
authors.lastname: Bianchi
authors.forename: Carlo
authors.initials: C
authors.lastname: Rossetti
authors.forename: Jacqueline
authors.initials: J
authors.lastname: French
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000927:Anticonvulsants; D017472:Receptors, Interleukin-1; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4