title: Inflammasome and cytokine blocking strategies in autoinflammatory disorders.
abstract: Autoinflammatory disorders are characterized by usually unprovoked recurrent episodes of features of inflammation caused by activation of the innate immune system. Many autoinflammatory disorders - the monogenetic defects in particular - are associated with alterations of inflammasomes. Inflammasomes are complex multimolecular structures, which respond to "danger" signals by activation of cytokines. Among these, IL-1 is the key player of the innate immune response and inflammation. Consequently, IL-1 blocking strategies are specific pathway targeting therapies in autoinflammatory diseases and applied in CAPS, colchicine-resistant FMF, TRAPS, HIDS and DIRA. A number of rare genetic disorders involve inflammasome malfunction resulting in enhanced inflammatory response. IL-1 inhibition to date is the most successful specific therapy in autoinflammatory disorders. Here, current treatment strategies in autoinflammatory disorders are reviewed with a focus on inflammasome and cytokine inhibition.
authors.affiliation: Division of Pediatric Rheumatology, Department of Pediatrics, University Children's Hospital Tuebingen, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Moll
authors.forename: Jasmin B
authors.initials: JB
authors.lastname: Kuemmerle-Deschner
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000494:pharmacology; D004789:Enzyme Activation; D056660:Hereditary Autoinflammatory Diseases / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D058847:Inflammasomes / Q000037:antagonists & inhibitors* / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D058847:Inflammasomes; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D011993:Recombinant Fusion Proteins; C541220:canakinumab; C531377:rilonacept; C547697:gevokizumab