Premium
Therapeutic potential of new antiinflammatory drugs
Author(s) -
Vezzani Annamaria,
Bartfai Tamas,
Bianchi Marco,
Rossetti Carlo,
French Jacqueline
Publication year - 2011
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2011.03242.x
Subject(s) - proinflammatory cytokine , receptor , tlr4 , epilepsy , downregulation and upregulation , signal transduction , pharmacology , medicine , neuroscience , biology , immunology , inflammation , microbiology and biotechnology , biochemistry , gene
Summary 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.