Mechanism of Action of Colchicine in the Treatment of Gout
Механизм действия колхицина при лечении подагры
2014-08-21
SCID: 54.1/u8tnr4te
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colchicinegouty arthritisinflammasome activationmicrotubule assemblymonosodium urate crystals
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Abstract (AI)
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. IMPLICATIONS: Colchicine has multiple mechanisms of action that affect inflammatory processes and result in its utility for treating and preventing acute gout flare. Other chronic inflammatory diseases that invoke these molecular pathways may represent new therapeutic applications for colchicine.
Key Findings
1
Because similar cellular processes occur in other chronic inflammatory diseases, colchicine may have therapeutic utility beyond gout, including osteoarthritis and cardiovascular disease.
2
By modulating multiple pro- and anti-inflammatory pathways, colchicine treats and prevents acute gout flares.
3
Colchicine prevents microtubule assembly, disrupting inflammasome activation, inflammatory-cell chemotaxis, leukotriene and cytokine generation, and phagocytosis.
4
Gouty arthritis involves multiple concurrent inflammatory pathways triggered by interactions between monosodium urate crystals and cell surfaces.
5
The review identifies multimodal colchicine mechanisms as a basis for potential applications in comorbid inflammatory conditions, while emphasizing these as prospective therapeutic uses.
Research Object
Colchicine in gout-associated acute inflammation and other chronic inflammatory conditions
Research Subject
Colchicine’s multimodal molecular mechanisms of action affecting inflammatory pathways and its therapeutic utility
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2014-08-21
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