Ying Ying Leung1, Laura Li Yao Hui2, Virginia B Kraus3. 1. Department of Rheumatology & Immunology, Singapore General Hospital, The Academia, Level 4, 20 College Rd, Singapore 169856; Department of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore. Electronic address: katyccc@hotmail.com. 2. Department of Rheumatology & Immunology, Singapore General Hospital, The Academia, Level 4, 20 College Rd, Singapore 169856. 3. Duke Molecular Physiology Institute and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC.
Abstract
OBJECTIVES: To review the literature and provide an update on the mechanisms of action and therapeutic uses of oral colchicine in arthritis and inflammatory conditions. METHODS: We performed PubMed database searches through June 2014 for relevant studies in the English literature published since the last update of colchicine in 2008. Searches encompassed colchicine mechanisms of action and clinical applications in medical conditions. A total of 381 articles were reviewed. RESULTS: The primary mechanism of action of colchicine is tubulin disruption. This leads to subsequent down regulation of multiple inflammatory pathways and modulation of innate immunity. Newly described mechanisms include various inhibitory effects on macrophages including the inhibition of the NACHT-LRRPYD-containing protein 3 (NALP3) inflammasome, inhibition of pore formation activated by purinergic receptors P2X7 and P2X2, and stimulation of dendritic cell maturation and antigen presentation. Colchicine also has anti-fibrotic activities and various effects on endothelial function. The therapeutic use of colchicine has extended beyond gouty arthritis and familial Mediterranean fever, to osteoarthritis, pericarditis, and atherosclerosis. CONCLUSION: Further understanding of the mechanisms of action underlying the therapeutic efficacy of colchicine will lead to its potential use in a variety of conditions.
OBJECTIVES: To review the literature and provide an update on the mechanisms of action and therapeutic uses of oral colchicine in arthritis and inflammatory conditions. METHODS: We performed PubMed database searches through June 2014 for relevant studies in the English literature published since the last update of colchicine in 2008. Searches encompassed colchicine mechanisms of action and clinical applications in medical conditions. A total of 381 articles were reviewed. RESULTS: The primary mechanism of action of colchicine is tubulin disruption. This leads to subsequent down regulation of multiple inflammatory pathways and modulation of innate immunity. Newly described mechanisms include various inhibitory effects on macrophages including the inhibition of the NACHT-LRRPYD-containing protein 3 (NALP3) inflammasome, inhibition of pore formation activated by purinergic receptors P2X7 and P2X2, and stimulation of dendritic cell maturation and antigen presentation. Colchicine also has anti-fibrotic activities and various effects on endothelial function. The therapeutic use of colchicine has extended beyond gouty arthritis and familial Mediterranean fever, to osteoarthritis, pericarditis, and atherosclerosis. CONCLUSION: Further understanding of the mechanisms of action underlying the therapeutic efficacy of colchicine will lead to its potential use in a variety of conditions.
Authors: Marzia Lotrionte; Giuseppe Biondi-Zoccai; Massimo Imazio; Davide Castagno; Claudio Moretti; Antonio Abbate; Pierfrancesco Agostoni; Antonio L Brucato; Pietro Di Pasquale; Marja Raatikka; Giuseppe Sangiorgi; Antonio Laudito; Imad Sheiban; Fiorenzo Gaita Journal: Am Heart J Date: 2010-10 Impact factor: 4.749
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