Critical role for macrophage migration inhibitory factor (MIF) in Ross River virus-induced arthritis and myositis

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Title Critical role for macrophage migration inhibitory factor (MIF) in Ross River virus-induced arthritis and myositis
Author Herrero, Lara; Nelson, Michelle; Srikiatkhachorn, Anon; Gu, Ran; Anantapreecha, Surapee; Fingerle-Rowson, Günter; Bucala, Richard; Morand, Eric; Santos, Leilani L.; Mahalingam, Suresh
Journal Name Proceedings of the National Academy of Sciences of USA
Year Published 2011
Place of publication United States
Publisher National Academy of Sciences
Abstract Arthrogenic alphaviruses, such as Ross River virus (RRV), chikungunya, Sindbis, mayaro and o'nyong-nyong viruses circulate endemically worldwide, frequently causing outbreaks of polyarthritis. The exact mechanisms of how alphaviruses induce polyarthritis remain ill defined, although macrophages are known to play a key role. Macrophage migration inhibitory factor (MIF) is an important cytokine involved in rheumatoid arthritis pathogenesis. Here, we characterize the role of MIF in alphavirus–induced arthritides using a mouse model of RRV-induced arthritis, which has many characteristics of RRV disease in humans. RRV-infected WT mice developed severe disease associated with up-regulated MIF expression in serum and tissues, which corresponded to severe inflammation and tissue damage. MIF-deficient (MIF−/−) mice developed mild disease accompanied by a reduction in inflammatory infiltrates and muscle destruction in the tissues, despite having viral titers similar to WT mice. In addition, reconstitution of MIF into MIF−/− mice exacerbated RRV disease and treatment of mice with MIF antagonist ameliorated disease in WT mice. Collectively, these findings suggest that MIF plays a critical role in determining the clinical severity of alphavirus–induced musculoskeletal disease and may provide a target for the development of antiviral pharmaceuticals. The prospect being that early treatment with MIF-blocking pharmaceuticals may curtail the debilitating arthritis associated with alphaviral infections.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1073/pnas.1101089108
Volume 108
Issue Number 29
Page from 12048
Page to 12053
ISSN 0027-8424
Date Accessioned 2012-03-13; 2012-04-10T23:44:14Z
Date Available 2012-04-10T23:44:14Z
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Humoural Immunology and Immunochemistry
URI http://hdl.handle.net/10072/44391
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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