Mechanism of Action of Colchicine in the Treatment of Gout

被引:392
作者
Dalbeth, Nicola [1 ]
Lauterio, Thomas J. [2 ]
Wolfe, Henry R. [3 ]
机构
[1] Univ Auckland, Dept Med, Auckland 1142, New Zealand
[2] URL Pharma Inc, Med Affairs, Philadelphia, PA USA
[3] Kyowa Kirin Pharma Inc, Princeton, NJ USA
关键词
colchicine; gout; inflammatory arthritis; mechanism of action; MONOSODIUM URATE CRYSTALS; PROINFLAMMATORY CYTOKINE PRODUCTION; INDUCED NEUTROPHIL ACTIVATION; RANDOMIZED CONTROLLED-TRIAL; INFLAMMATION IN-VIVO; GROWTH-FACTOR BETA-1; LOW-DOSE COLCHICINE; C-REACTIVE PROTEIN; NALP3; INFLAMMASOME; NLRP3;
D O I
10.1016/j.clinthera.2014.07.017
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Purpose: The aims of this article were to systematically review the literature about the mechanism of action of colchicine in the multimodal pathology of acute inflammation associated with gout and to consider the clinical utility of colchicine in other chronic inflammatory diseases. Methods: The English-language literature on PubMed was searched for articles published between 1990 and October 2013, with a cross-reference to citations across all years. Relevant articles pertaining to the mechanism of action of colchicine and the clinical applications of colchicine in gout and other inflammatory conditions were identified and reviewed. Findings: The molecular pathology of acute inflammation associated with gouty arthritis involves several concurrent pathways triggered by a variety of interactions between monosodium urate crystals and the surface of cells. Colchicine modulates multiple pro- and antiinflammatory pathways associated with gouty arthritis. Colchicine prevents microtubule assembly and thereby disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis. Many of these cellular processes can be found in other diseases involving chronic inflammation. The multimodal mechanism of action of colchicine suggests potential efficacy of colchicine in other comorbid conditions associated with gout, such as osteoarthritis and cardiovascular disease. (C) 2014 The Authors. Published by Elsevier HS Journals, Inc.
引用
收藏
页码:1465 / 1479
页数:15
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