title: Colchicine--Update on mechanisms of action and therapeutic uses.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Ying Ying
authors.initials: YY
authors.lastname: Leung
authors.affiliation: Department of Rheumatology & Immunology, Singapore General Hospital, The Academia, Level 4, 20 College Rd, Singapore 169856.
authors.forename: Laura Li
authors.initials: LL
authors.lastname: Yao Hui
authors.affiliation: Duke Molecular Physiology Institute and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC.
authors.forename: Virginia B
authors.initials: VB
authors.lastname: Kraus
mesh_terms: D015210:Arthritis, Gouty / Q000188:drug therapy / Q000378:metabolism; D003078:Colchicine / Q000627:therapeutic use*; D006073:Gout / Q000188:drug therapy* / Q000378:metabolism; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D014404:Tubulin / Q000378:metabolism*
chemical_list: D006074:Gout Suppressants; D014404:Tubulin; D003078:Colchicine
keywords: Colchicines; Inflammation; Mechanism of action; Pharmacokinetics; Therapeutic use