title: The inflammatory process of gout and its treatment.
abstract: Gouty arthritis is a characteristically intense acute inflammatory reaction that erupts in response to articular deposits of monosodium urate (MSU) crystals. Important recent molecular biologic advances in this field have given us a clear picture of the mechanistic basis of gouty inflammation. The innate immune inflammatory response is critically involved in the pathology of gout. Specifically, MSU crystals promote inflammation directly by stimulating cells via Toll-like receptor signaling and by providing a surface for cleavage of C5 and formation of complement membrane attack complex (C5b-9), culminating in secretion of cytokines, chemokines, and other inflammatory mediators with a dramatic influx of neutrophils into the joint. Despite the detailed mechanistic picture for gouty inflammation, there are no placebo-controlled, randomized clinical studies for any of the therapies commonly used, although comparative studies have demonstrated that many nonsteroidal anti-inflammatory drugs are equivalent to indomethacin with respect to controlling acute gouty attacks. In general, the first line of anti-inflammatory therapy for acute gout is nonsteroidal anti-inflammatory drugs, and the selective cyclo-oxygenase-2 inhibitor celecoxib can be used where appropriate. The second line of treatment is glucocorticosteroids, given systemically (oral, intravenous, or intramuscular) or intra-articularly. Alternatively, synthetic adrenocorticotropic hormone is effective, partly via induction of adrenal glucocorticosteroids and partly via rapid peripheral suppression of leukocyte activation by melatonin receptor 3 signaling. The third line of treatment is oral colchicine, which is highly effective when given early in an acute gouty attack, but it is poorly tolerated because of predictable gastrointestinal side effects.
authors.affiliation: Department of Medicine and Division of Clinical Pharmacology, New York University School of Medicine, New York, New York, USA. Bruce.Cronstein@nyumc.org
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Cronstein
authors.forename: Robert
authors.initials: R
authors.lastname: Terkeltaub
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D015210:Arthritis, Gouty / Q000188:drug therapy / Q000503:physiopathology*; D002986:Clinical Trials as Topic; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D006073:Gout / Q000503:physiopathology* / Q000628:therapy*; D006074:Gout Suppressants / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D014527:Uric Acid / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D006074:Gout Suppressants; D014527:Uric Acid