New therapeutic target in inflammatory disease: macrophage migration inhibitory factor
- 16 June 2005
- journal article
- review article
- Published by Wiley in Internal Medicine Journal
- Vol. 35 (7), 419-426
- https://doi.org/10.1111/j.1445-5994.2005.00853.x
Abstract
The cytokine macrophage migration inhibitory factor (MIF) participates in fundamental events in innate and adaptive immunity. The profile of activities of MIF in vivo and in vitro is strongly suggestive of a role for MIF in the pathogenesis of many inflammatory diseases, including rheumatoid arthritis (RA), and hence antagonism of MIF is suggested as a potential therapeutic strategy in inflammatory disease. The best developed case for therapeutic antagonism of MIF is in RA. In RA, MIF is abundantly expressed in serum and synovial tissue. MIF induces synovial expression of key pro‐inflammatory genes, regulates the function of endothelial cells and leucocytes, and is implicated in the control of synoviocyte proliferation and apoptosis via direct effects on the expression of the tumour suppressor protein p53. In animal models of RA, anti‐MIF antibodies or genetic MIF deficiency are associated with significant inhibition of disease. A similar case has been made, for example using MIF‐deficient mice, in models of atheroma, colitis, multiple sclerosis and other inflammatory diseases. The relationship with p53 also means MIF may be important in the link between inflammatory disease and cancer, such as is seen in RA or colitis. MIF also has a unique relationship with glucocorticoids, in that despite antagonizing their effects, the expression of MIF is in fact induced by glucocorticoids. Thus, MIF functions as a physiological counter‐regulator of the anti‐inflammatory effects of glucocorticoids. This may be entrained by selective activation of mitogen‐activated protein kinases rather than nuclear factor kappa B. Therapeutic MIF antagonism may therefore provide a specific means of ‘steroid sparing’. Exploitation of antibody, soluble receptor or small molecule technologies may soon lead to the ability to test in the clinic the importance of MIF in human inflammatory diseases. (Intern Med J 2005; 35: 419–426)Keywords
This publication has 78 references indexed in Scilit:
- Reduced leukocyte–endothelial cell interactions in the inflamed microcirculation of macrophage migration inhibitory factor–deficient miceArthritis & Rheumatism, 2004
- Inhibition of joint inflammation and destruction induced by anti-type II collagen antibody/lipopolysaccharide (LPS)-induced arthritis in mice due to deletion of macrophage migration inhibitory factor (MIF)Cytokine, 2004
- Regulation of p53 by macrophage migration inhibitory factor in inflammatory arthritisArthritis & Rheumatism, 2003
- Regulation of macrophage migration inhibitory factor by endogenous glucocorticoids in rat adjuvant-induced arthritisArthritis & Rheumatism, 2000
- Evidence for a role of macrophage migration inhibitory factor in psoriatic skin diseaseBritish Journal of Dermatology, 1999
- Macrophage migration inhibitory factor in IgA nephropathyKidney International, 1998
- Advances in the understanding of neuroendocrine function in rheumatic diseaseAustralian and New Zealand Journal of Medicine, 1996
- Cloning and sequencing of a cDNA encoding rat d‐dopachrome tautomeraseFEBS Letters, 1995
- Purification, Bioactivity, and Secondary Structure Analysis of Mouse and Human Macrophage Migration Inhibitory Factor (MIF)Biochemistry, 1994
- Antigen and Mitogen Induced Production of Macrophage Migration Inhibitory Factor in the MouseInternational Archives of Allergy and Immunology, 1979