Development of chronic colitis is dependent on the cytokine MIF

Abstract

The cytokine macrophage-migration inhibitory factor (MIF) is secreted by a number of cell types upon induction by lipopolysaccharide (LPS). Because colitis is dependent on interplay between the mucosal immune system and intestinal bacteria, we investigated the role of MIF in experimental colitis. MIF-deficient mice failed to develop disease, but reconstitution of MIF-deficient mice with wild-type innate immune cells restored colitis. In addition, established colitis could be treated with anti-MIF immunoglobulins. Thus, murine colitis is dependent on continuous MIF production by the innate immune system. Because we found increased plasma MIF concentrations in patients with Crohn's disease, these data suggested that MIF is a new target for intervention in Crohn's disease.

Macrophage migration inhibitory factor (MIF) gene polymorphism is associated with susceptibility to but not severity of inflammatory polyarthritis

“…Several investigators have suggested the use of anti-MIF therapy. [16][17][18] Our data support such a use in the potential treatment of patients with IP.…”

Identification of macrophage migration inhibitory factor and human neutrophil peptides 1–3 as potential biomarkers for gastric cancer

“…Mechanisms involved include activation of the MAP kinase pathways through CD74 and CD44 (Shi et al, 2006), suppression of p53 (Hudson et al, 1999;Fingerle-Rowson et al, 2003) and downregulation of NKG2D enhancing immune evasion by cancer cells (Krockenberger et al, 2008). As with HNPs 1 -3, MIF may lack specificity for gastric cancer as it has been reported as elevated in the plasma of patients with ulcerative colitis and Crohn's disease (de Jong et al, 2001;Murakami et al, 2001). However, preliminary work in our laboratory suggests a degree of disease specificity: serum MIF is also elevated in European patients with hepatocellular carcinoma (relative to our 29 Japanese noncancer controls), but is not elevated in patients with lung or pancreas cancer or individuals without cancer (n X 30 per group, data not shown).…”

Macrophage migration inhibitory factor is essential for allergic asthma but not for Th2 differentiation

“…Once released, MIF can counterregulate the anti-inflammatory effects of steroids on cytokine production [15]. By means of antibody neutralization or gene deletion it has been demonstrated that MIF plays an important role in the pathogenesis of several inflammatory disorders, such as sepsis, glomerulonephritis, arthritis, colitis, encephalomyelitis, leishmaniasis and atherosclerosis [11,12,[16][17][18][19][20][21][22][23]. Increased MIF expression has also been observed in patients suffering from inflammatory diseases including sepsis, rheumatoid arthritis, acute respiratory distress syndrome (ARDS) and asthma [11,12,18,[24][25][26][27][28][29].…”