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Mechanisms of Disease: macrophage migration inhibitory factor in SLE, RA and atherosclerosis

Nature Clinical Practice Rheumatology volume 4, pages 98–105 (2008)Cite this article

Abstract

The past decade has seen the emergence of two new paradigms in inflammatory disease: first, cardiovascular complications of atherosclerosis are markedly increased in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE); and second, inflammatory mechanisms are important in the pathogenesis of atherosclerosis. These concurrent developments have lead to the concept that inflammatory mediators operative in RA and SLE might be causal in the accelerated atherosclerosis observed, a concept supported by clinical studies showing that this acceleration is not fully explained by traditional vascular risk factors. Separate lines of evidence implicate the cytokine macrophage migration inhibitory factor (MIF) in RA, SLE, and atherosclerosis. Several reports have revealed definitive in vivo evidence of the activity of MIF in a model of SLE, demonstrated a novel role for MIF in monocyte/macrophage recruitment, and showed that MIF regulates a key mediator of inflammatory cell activation. Together with evidence that MIF circulates in increased concentrations in patients with RA and SLE, this information suggests that in addition to contributing to each disease, MIF might contribute directly to the acceleration of atherosclerosis in RA and SLE.

Key Points

  • There is an increased burden of cardiovascular disease in patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), which is incompletely explained by traditional risk factors

  • Inflammation has a critical role in the molecular pathogenesis of atherosclerosis

  • Macrophage migration inhibitory factor (MIF) has been demonstrated to be involved in the pathogenesis of each of RA, SLE and atherosclerosis, and increased levels of MIF in patients with RA and SLE might contribute to accelerated atherosclerosis in those diseases

  • New reports demonstrate that MIF is involved in monocyte/macrophage recruitment, via effects on CC-chemokine ligand 2 and CXC-chemokine receptor 2 in lupus nephritis, postcapillary venules and arterial walls

  • MIF has been shown to be a key negative regulator of MAP kinase phosphatase-1

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Figure 1: Potential roles for macrophage migration inhibitory factor in atherosclerosis.

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Authors and Affiliations

  1. S Ayoub is a doctoral fellow in Rheumatology at Monash Medical Centre and Monash University, MJ Hickey is a Senior Research Officer at the Centre for Inflammatory Diseases, Monash University, and EF Morand is Associate Professor of Medicine at Monash University and Deputy Director of Rheumatology at Monash Medical Centre, Melbourne, Australia.,

    Sally Ayoub, Michael J Hickey & Eric F Morand

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  1. Sally Ayoub
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Correspondence to Eric F Morand.

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Competing interests

EF Morand is an employee and shareholder of Cortical Pty Ltd, a company engaged in the discovery of MIF antagonist compounds. The other authors declared no competing interests.

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Ayoub, S., Hickey, M. & Morand, E. Mechanisms of Disease: macrophage migration inhibitory factor in SLE, RA and atherosclerosis. Nat Rev Rheumatol 4, 98–105 (2008). https://doi.org/10.1038/ncprheum0701

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