Blockade of colony stimulating factor-1 (CSF-1) leads to inhibition of DSS-induced colitis

被引:48
作者
Marshall, Diane [1 ]
Cameron, James [1 ]
Lightwood, Daniel [1 ]
Lawson, Alastair D. G. [1 ]
机构
[1] UCB, Celltech Ctr Excellence Antibody Res, Slough SL1 4EN, Berks, England
关键词
CSF-1; experimental colitis; macrophage; antibody;
D O I
10.1002/ibd.20055
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Intestinal inflammation associated with inflammatory bowel disease (IBD) is typically characterized by an inflammatory cell infiltrate and pro-inflammatory cytokine production. Of particular interest, the frequency of colony stimulating factor-1 (CSF-1)-expressing cells is increased in active lesions. In this study, we have investigated the role of CSF-1 in mucosal inflammation, using a murine model of colitis induced by dextran sulfate sodium (DSS). Methods: A neutralizing anti-CSF-1 antibody was administered to BaIb/c mice that received DSS in their drinking water. Signs of colitis, such as clinical disease score, cellular infiltrate, and cytokine production, were assessed. Results: Administration of a neutralizing anti-CSF-1 antibody significantly inhibited DSS-induced colitis. Clinical symptoms, such as weight loss and the appearance of diarrhea or fecal blood, were reduced by CSF-1 blockade; histologic scores were also improved. The cellular infiltrate of macrophages and T cells was inhibited and a trend toward reduced production of pro-inflammatory cytokines was noted. Conclusions: This is the first study to demonstrate that CSF-1 plays an important role in mediating intestinal mucosal inflammation and therefore may prove to be an attractive therapeutic target for intestinal diseases such as inflammatory bowel disease.
引用
收藏
页码:219 / 224
页数:6
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