Macrophage migration inhibitory factor activates antigen-presenting dendritic cells and induces inflammatory cytokines in ulcerative colitis

Abstract

SUMMARY The level of macrophage migration inhibitory factor (MIF) and the functions of dendritic cells (DC) are up-regulated in the peripheral blood, and the numbers of MIF-expressing cells and mature DC are increased at the colonic mucosa from patients with ulcerative colitis (UC). However, a functional relationship between MIF and DC, and the role of MIF in the pathogenesis of UC, are not clear. In this study, we showed that a pure population of peripheral blood DC is a new and still unknown source of MIF. DC from UC patients produced significantly higher levels of MIF (17·5 ± 9·8 ng/ml, n = 10) compared with patients with Crohn's disease (CD) (4·6 ± 2·5 ng/ml, n = 5, P < 0·01) and control subjects (5·0 ± 2·6 ng/ml, n = 10, P < 0·01). A double immunofluorescence study revealed the expression of MIF by CD83-positive mature DC at the colonic mucosa from UC patients. Blood DC treated with high amounts of MIF (500 ng/ml) showed a significantly higher stimulatory capacity (43287 ± 5998 CPM, n = 5) in an allogenic mixed leucocyte reaction compared with untreated DC (27528 ± 8823 CPM, n = 5, P < 0·05). Study of intracellular cytokine expression showed that MIF induced significant levels of interleukin (IL)-1β and IL-8 in monocytes and DC from UC and CD patients. These results showing the capacity of MIF to induce increased functional capacity of DC, and to produce IL-1β and IL-8 from monocytes and DC, indicate a role of MIF in the induction and/or perpetuation of the inflammatory environment in UC.