Expression of macrophage migration inhibitory factor in diffuse systemic sclerosis

Abstract

Objective: To evaluate whether, in patients with the diffuse form of systemic sclerosis (dSSc), macrophage migration inhibitory factor (MIF) production is dysregulated. Methods: 10 patients with dSSc and 10 healthy controls, matched for age and sex, were studied. MIF expression was evaluated by immunohistochemistry on formalin fixed skin biopsies of patients with dSSc and controls. MIF levels were assayed in the sera and in the supernatants of skin cultured fibroblasts by a colorimetric sandwich enzyme linked immunosorbent assay (ELISA). MIF concentrations in culture medium samples and in serum samples were compared by Student's two tailed t test for unpaired data. Results: Anti-MIF antibody immunostained the basal and mainly suprabasal keratinocytes. Small perivascular clusters of infiltrating mononuclear cells were positive; scattered spindle fibroblast-like cells were immunostained in superficial and deep dermal layers. The serum concentrations of MIF in patients with dSSc (mean (SD) 10705.6 (9311) pg/ml) were significantly higher than in controls (2157.5 (1288.6) pg/ml; p=0.011); MIF levels from dSSc fibroblast cultures (mean (SD) 1.74 (0.16) ng/2×10 5 cells) were also significantly higher than in controls (0.6 (0.2) ng/2×10 5 cells; p=0.008). Conclusion: These results suggest that MIF may be involved in the amplifying proinflammatory loop leading to scleroderma tissue remodelling.

Analysis of serum macrophage migration inhibitory factor and D‐dopachrome tautomerase in systemic sclerosis

“…Here, we examined concentrations of serum MIF and DDT in SSc and HC, in order to determine their clinical associations in SSc. In line with previous studies,9, 15 we found a significant increase in serum MIF concentrations in SSc patients compared to HC. However, there was no significant difference in serum DDT between SSc and HC.…”

Role of macrophage migration inhibitory factor (MIF) in the skin

“…Foote et al examined the associations between serum MIF concentrations and diseaserelated indices of systemic lupus erythematosus (SLE) and corticosteroid use [31]: serum MIF concentrations were positively associated with SLE disease activity and with corticosteroid dose [31]. In view of its multiple functions, MIF may be a critical mediator of inflammation and damage in SLE, and that targeting MIF may offer considerable therapeutic benefits for treating this disease [32].…”

Clinical Relevance of Cytokines, Chemokines and Adhesion Molecules in Systemic Vasculitis

“…Several cell populations, including T cells (Bacher et al 1996), macrophages/monocytes (Calandra et al 1994), synovial fibroblasts (Leech et al 1999) and endothelial cells (Nishihira et al 1998) express and secrete MIF. Furthermore, MIF is implicated in various inflammatory and immune-mediated diseases, including RA (Leech, Metz et al 1999;Ayoub et al 2008), SLE (Hoi et al 2003;Foote et al 2004), scleroderma (Selvi et al 2003) and inflammatory bowel diseases (de Jong et al 2001). Serum MIF levels are also increased in systemic vasculitis, including WG and AAV (Ohwatari et al 2001;Becker et al 2006).…”