Amelioration of dextran sulfate sodium-induced colitis by anti-macrophage migration inhibitory factor antibody in mice.
BACKGROUND & AIMS: We investigated the effects of macrophage migration inhibitory factor ( MIF) antibodies in experimental colitis-induced dextran sulfate sodium (DSS) and trinitrobenzenesulfonic acid (TNBS) and examined whether plasma levels of MIF were elevated in patients with inflammatory bowel disease (IBD). METHODS: BALB/c or C57BL/6 mice were fed 4% DSS in their drinking water for up to 7 days with and without administration of an anti- MIF antibody every 2 days. The severity of inflammation in the cecum and colon was assessed by clinical signs and histologic scoring. Tissue levels of MIF, tumor necrosis factor (TNF)-alpha, interferon gamma ( IFN-gamma), interleukin (IL)-4, and matrix metalloproteinase (MMP)-13 messenger RNA (mRNA) were measured. The effects of anti- MIF antibody on chronic colitis induced by TNBS was assessed in BALB/c mice. Plasma MIF concentrations were assayed in patients with Crohn's disease, ulcerative colitis, and healthy controls. RESULTS: During DSS-induced colitis, colonic MIF mRNA expression was increased. Clinical signs and histopathologic features were significantly improved in animals given anti- MIF antibody. DSS-induced up-regulation of colonic TNF-alpha and IFN-gamma were significantly suppressed in animals given the anti- MIF antibody. Colonic IL-4 was decreased during DSS but restored to baseline by the anti- MIF antibody. The anti- MIF antibody prevented MMP-13 up-regulation by DSS and ameliorated TNBS colitis. Plasma MIF was elevated in patients with Crohn's disease or ulcerative colitis compared with healthy controls. CONCLUSIONS: We conclude that anti- MIF antibodies reduce the severity of experimental colitis and limit the up-regulation of Th1-type cytokines. Anti- MIF antibodies are of potential therapeutic use in IBD.[1]References
- Amelioration of dextran sulfate sodium-induced colitis by anti-macrophage migration inhibitory factor antibody in mice. Ohkawara, T., Nishihira, J., Takeda, H., Hige, S., Kato, M., Sugiyama, T., Iwanaga, T., Nakamura, H., Mizue, Y., Asaka, M. Gastroenterology (2002) [Pubmed]
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