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: Anjana Singh, Lin Leng, Juan Fan, Mieczyslaw Gajda, Rolf Bräuer, Günter Fingerle-Rowson, Richard Bucala, Harald Illges
• Journal: Rheumatology international (Rheumatol Int) Vol. 33 Issue 9 Pg. 2301-8 (Sep 2013) ISSN: 1437-160X [Electronic] Germany
• PMID: 23503937 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Macrophage Migration-Inhibitory Factors
• Intramolecular Oxidoreductases
• Mif protein, mouse

Topics

• Animals
• Arthritis, Experimental (etiology)
• Cytokines (blood)
• Disease Models, Animal
• Intramolecular Oxidoreductases (physiology)
• Macrophage Migration-Inhibitory Factors (physiology)
• Macrophages (physiology)
• Mice
• Mice, Inbred C57BL