title: Macrophage migration inhibitory factor: a potential therapeutic target for rheumatoid arthritis.
abstract: Macrophage migration inhibitory factor (MIF) is originally identified in the culture medium of activated T lymphocytes as a soluble factor that inhibits the random migration of macrophages. MIF is now recognized as a multipotent cytokine involved in the regulation of immune and inf lammatory responses. In rheumatoid arthritis (RA), MIF promotes inf lammatory responses by inducing proinflammatory cytokines and tissue-degrading molecules, promoting the proliferation and survival of synovial fibroblasts, stimulating neutrophil chemotaxis, and regulating angiogenesis and osteoclast differentiation. Expression of MIF in synovial tissue and synovial fluid levels of MIF are elevated in RA patients. Specifically, MIF levels correlate with RA disease activity and high levels are associated with bone erosion. In animal models of RA, the genetic and therapeutic inhibition of MIF has been shown to control inflammation and bone destruction. Based on the role of MIF in RA pathogenesis, small molecular inhibitors targeting it or its receptor pathways could provide a new therapeutic option for RA patients.
authors.affiliation: Convergent Research Consortium for Immunologic Disease, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Kyoung-Woon
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Hae-Rim
authors.initials: HR
authors.lastname: Kim
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018501:Antirheumatic Agents; D018836:Inflammation Mediators; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: Arthritis, rheumatoid; Inflammation; Macrophage migration-inhibitory factors; Small molecular inhibitor