title: Macrophage-derived, macrophage migration inhibitory factor (MIF) is necessary to induce disease in the K/BxN serum-induced model of arthritis.
abstract: Rheumatoid arthritis (RA) is characterized by the interaction of multiple mediators, among the most important of which are cytokines. In recent years, extensive studies demonstrate a pivotal role for one cytokine, macrophage migration inhibitory factor (MIF), in fundamental events in innate and adaptive immunity. MIF has now been demonstrated to be involved in the pathogenesis of many diseases, but in the case of RA the evidence for a role of MIF is very strong. MIF is abundantly expressed in the sera of RA patients and in RA synovial tissue correlating with disease activity. MIF-deficient mice were used to induce arthritis by serum transfer from K/BxN mice. K/BxN serum transfer arthritis was markedly attenuated in MIF(-) mice, with reduction in clinical index and histological severity as well as decrease in synovial cytokines. Macrophage transfers were done to investigate the specific role of macrophage-derived MIF. We show that adoptive transfer of wild-type macrophages into MIF(-) mice restores the sensitivity of MIF(-) mice to arthritis development, and this affect was associated with a restoration in serum IL-1β and IL-6 production. These results indicate that MIF plays a critical role in inflammation and joint destruction in K/BxN serum-induced arthritis and that the systemic expression of MIF by a subpopulation of macrophages is necessary and sufficient for the full development of arthritis.
authors.affiliation: Department of Natural Sciences, Immunology and Cell Biology, University of Applied Sciences, von-Liebig-Str. 20, 53359 Rheinbach, Germany.
authors.forename: Anjana
authors.initials: A
authors.lastname: Singh
authors.forename: Lin
authors.initials: L
authors.lastname: Leng
authors.forename: Juan
authors.initials: J
authors.lastname: Fan
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Gajda
authors.forename: Rolf
authors.initials: R
authors.lastname: Bräuer
authors.forename: Günter
authors.initials: G
authors.lastname: Fingerle-Rowson
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
authors.forename: Harald
authors.initials: H
authors.lastname: Illges
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D019746:Intramolecular Oxidoreductases / Q000502:physiology*; D008263:Macrophage Migration-Inhibitory Factors / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D016207:Cytokines; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse