Elevated serum levels of macrophage migration inhibitory factor and their significant correlation with rheumatoid vasculitis disease activity

Abstract

Macrophage migration inhibitory factor (MIF) is recognized to be an important mediator in several inflammatory disorders, including rheumatoid arthritis (RA) and vasculitis. To evaluate the role of MIF in rheumatoid vasculitis (RV), we determined serum levels of MIF by enzyme-linked immunosorbent assay in RA patients with and without vasculitis and assessed their relationship to disease activity. Serum was obtained from 95 RA patients during active disease states [49 without vasculitis, 35 with extra-articular manifestations without histologically proven vasculitis, and 11 with histologically proven vasculitis] and from 22 healthy individuals. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). MIF levels were significantly higher in RA patients than in controls. Moreover, MIF levels were significantly higher in RA patients with vasculitis than in those without vasculitic complications. In all RA patients, a statistically significant positive correlation was observed between serum MIF levels and each of the following: serum levels of C-reactive protein, rheumatoid factor, and thrombomodulin; and the erythrocyte sedimentation rate. In the RV group, the elevation of MIF levels correlated with the BVAS. Our findings suggest that MIF may serve as an additional serologic inflammatory marker of disease activity in RV, and it may be implicated in the pathogenesis of RV.

Elevated Serum Levels of Macrophage Migration Inhibitory Factor Are Associated with Progressive Chronic Cardiomyopathy in Patients with Chagas Disease

“…Interestingly, recent studies demonstrated that coxsackievirus B3-induced myocarditis as well as human diabetes-linked LV dysfunction correlate with increased MIF concentration in the bloodstream [69], [70]. Also, high levels of MIF showed good correlation with CRP in the sera from patients with rheumatoid arthritis [71].…”

Isopsoralen ameliorates rheumatoid arthritis by targeting MIF

“…Elevated levels of MIF expression were observed in synovial tissues and synovial fluids from RA patients compared to osteoarthritis (OA) patients or healthy volunteers [ 37 ]. Specifically, the expression of MIF was closely related to the activity of RA, and its expression at higher levels indicated more severe bone erosion [ 38 ]. Functionally, MIF was required for sustaining inflammatory responses by inducing the production of proinflammatory cytokines and tissue-degrading molecules, promoting the proliferation and survival of synovial fibroblasts, stimulating the chemotaxis of neutrophils, and increasing angiogenesis and osteoclast differentiation.…”

The Novel Role of MIF in the Secretion of IL-25, IL-31, and IL-33 from PBMC of Patients with Rheumatoid Arthritis

“…RA is a rheumatic disease characterized by synovitis and systemic inflammation in which a complex network of different cytokines is known to be involved in tissue damage, but the exact mechanism of disease pathogenesis is still unknown [ 1 ]. The cytokine MIF has been associated with the inflammatory process in RA due to its important regulatory role in the immune response [ 2 ]. Regarding this, it has been described that MIF can be stimulated by the persistent proinflammatory response in RA, and that it can promote the activation of phospholipase A2 (PLA2) and the production of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in multiple immune cells that are associated with joint inflammation and the promotion of the production of proinflammatory cytokines that play a crucial role in early and established RA, such as TNF-α, interferon (IFN)-γ, IL-1β, IL-6 [ 3 ], and IL-17 [ 4 ].…”

“…Rheumatoid arthritis (RA) is an autoimmune chronic disease associated with high levels of proinflammatory cytokines, secreted mainly by mononuclear cells such as T lymphocytes and macrophages [ 1 ]. Macrophage migration inhibitory factor (MIF) is an inflammatory mediator that participates in the regulation of the immune response and plays an important role in the joint destruction process in RA [ 2 ]. In macrophages and synovial fibroblasts, MIF induces the expression of tissue-destructive cytokines and mediators, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, and some matrix metalloproteinases (MMP) such as MMP-1 and MMP-3 [ 3 ].…”