Amelioration of dextran sulfate sodium–induced colitis by anti-macrophage migration inhibitory factor antibody in mice

doi:10.1053/gast.2002.34236

Gastroenterology

Volume 123, Issue 1, July 2002, Pages 256-270

https://doi.org/10.1053/gast.2002.34236 Get rights and content

Abstract

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)-α, interferon gamma (IFN-γ), 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-α and IFN-γ 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.

GASTROENTEROLOGY 2002;123:256-270

Section snippets

Materials

The following materials were obtained from commercial sources: rabbit immunoglobulin (IgG fraction) from ICN (Aurora, OH); dextran sulfate sodium (molecular mass, 5 kilodaltons; 15%–17% sulfur content) from Wako (Osaka, Japan); GenePure from Nippon Gene (Toyama, Japan); random primer DNA labeling kit from Takara (Kyoto, Japan); 2,4,6-trinitrobenzenesulfonic acid (TNBS) and cocktail of protease inhibitors containing 4-(2-aminoethylbenzenesulfonyl fluoride, pepstatin A,

Time course study of circulating MIF and TNF-α levels

The plasma MIF level of the DSS-treated BALB/c mice was determined at days 0, 1, 3, 5, and 7 after DSS administration. The plasma MIF level before DSS treatment was 78.5 ±9.2 ng/mL and changed minimally until day 5 after DSS, but markedly increased at day 7 after DSS (141.0 ± 8.1 ng/mL) (Figure 1).

. Time course of plasma MIF level of DSS-induced colitis in BALB/c mice. Mice were killed before and at 1, 3, 5, and 7 days after administration of 4% DSS solution. Each point represents the mean ±

Discussion

Ulcerative colitis and Crohn's disease, representatives of IBD, are chronic inflammatory diseases; however, their precise etiologies remain to be elucidated. To investigate their pathogenic mechanisms, several experimental models of IBD have been described.⁴¹ Among these, the DSS-induced colitis model has been widely used. DSS-induced colitis in rodents has been recommended for preclinical testing for new therapeutic methods for IBD and has a number of advantages, including the ability to

Acknowledgements

The authors thank Somako Tone and Asagi Matsumura for their excellent technical assistance.

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^☆: Address requests for reprints to: Jun Nishihira, M.D., Central Research Institute, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060, Japan. e-mail: [email protected]; fax: (81) 11-706-7864.

^☆☆: Supported by a Grant-in-Aid for research (no. 12213008) from the Ministry of Education, Science and Culture of Japan.

View full text

Basic–Alimentary TractAmelioration of dextran sulfate sodium–induced colitis by anti-macrophage migration inhibitory factor antibody in mice☆,☆☆

Abstract

Section snippets

Materials

Time course study of circulating MIF and TNF-α levels

Discussion

Acknowledgements

Inflammatory bowel disease

N Engl J Med

Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases

Am J Gastroenterol

Role of cytokines in the pathogenesis of inflammatory bowel disease

Annu Rev Med

Neutralization of endogenous IL-1 receptor antagonist exacerbates and prolongs inflammation in rabbit immune colitis

J Clin Invest

Recent developments in the medical therapy of inflammatory bowel disease

Curr Opin Gastroenterol

Blockade of interleukin-6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in Crohn disease and experimental colitis in vivo

Nat Med

Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2)

Gastroenterology

Randomised controlled trial of CDP571 antibody to tumor necrosis factor-alpha in Crohn's disease

Lancet

Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease

Gastroenterology

Mechanism of a reaction in vitro associated with delayed-type hypersensitivity

Science

Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction

Proc Natl Acad Sci U S A

The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor

J Exp Med

Identification of macrophage migration inhibitory factor (MIF) in human skin and its immmunohistochemical localization

FEBS Lett

Identification and immunohistochemical localization of macrophage migration inhibitory factor in human cornea

FEBS Lett

Identification of macrophage migration inhibitory factor in murine neonatal calvariae and osteoblasts

Immunology

Identification of macrophage migration inhibitory factor in human leukemia HL-60 cells and its induction by lipopolysaccharide

Biochem Mol Biol Int

Migration inhibitory factor expression in experimentally induced endotoxemia

Am J Pathol

MIF rediscovered: pituitary hormone and glucocorticoid-induced regulator of cytokine production

FASEB J

Macrophage migration inhibitory factor (MIF): its essential role in the immune system and cell growth

J Interferon Cytokine Res

MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia

Nature

MIF as a glucocorticoid-induced modulator of cytokine production

Nature

An essential regulatory role for macrophage migration inhibitory factor in T-cell activation

Proc Natl Acad Sci U S A

Novel pathophysiological aspects of macrophage migration inhibitory factor (review)

Int J Mol Med

Effect of anti-macrophage migration inhibitory factor antibody on LPS-induced pulmonary neutrophil accumulation

Am J Respir Crit Care Med

Regulatory role for macrophage migration inhibitory factor in acute respiratory distress syndrome

Nat Med

Basic–Alimentary Tract
Amelioration of dextran sulfate sodium–induced colitis by anti-macrophage migration inhibitory factor antibody in mice☆,☆☆