title: [New knowledge on the pathophysiology and therapy of gout].
abstract: Gout is caused by the deposition of monosodium urate crystals (MSU) in tissue and provokes a local inflammatory reaction. It is the most common form of inflammatory arthritis in the elderly. The formation of MSU crystals is facilitated by hyperuricemia. In the last two decades, both hyperuricemia and gout have increased markedly and similar trends in the epidemiology of the metabolic syndrome have been observed. Recent studies provide new insights into uric acid metabolism in the kidneys as well as possible links between hyperuricemia and hypertension. MSU crystals provoke inflammation by activating leukocytes to produce inflammatory cytokines and other inflammatory mediators. The uptake of MSU crystals by monocytes involves interactions with Toll-like receptors (TLR-2 and TLR-4) and CD14, components of the innate immune system. Intracellularly, MSU crystals activate inflammasomes to activate pro-IL-1 (interleukin 1) processing to yield mature IL-1beta. The inflammatory effects of MSU are IL-1-dependent and can be blocked by IL-1 inhibitors. These advances provide new therapeutic targets to treat hyperuricemia and gout.
authors.affiliation: Service de Rhumatologie, Departement de Médicine, CHU Vaudois, University of Lausanne, 1011, Lausanne, Schweiz. AlexanderKai-Lik.So@chuv.ch
authors.forename: A
authors.initials: A
authors.lastname: So
mesh_terms: D000818:Animals; D015210:Arthritis, Gouty / Q000188:drug therapy / Q000503:physiopathology*; D004727:Endothelium / Q000503:physiopathology; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D007668:Kidney / Q000503:physiopathology; D007964:Leukocytosis; D009000:Monocytes / Q000502:physiology; D013583:Synovial Membrane / Q000503:physiopathology; D014527:Uric Acid / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D014527:Uric Acid