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

Inflamm Bowel Dis. 2007 Feb;13(2):219-24. doi: 10.1002/ibd.20055.

Abstract

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-l)-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 Balb/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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Cell Movement
  • Colitis / chemically induced
  • Colitis / metabolism
  • Colitis / pathology*
  • Colon / metabolism
  • Colon / pathology
  • Cytokines / metabolism
  • Dextran Sulfate
  • In Vitro Techniques
  • Macrophage Colony-Stimulating Factor / immunology
  • Macrophage Colony-Stimulating Factor / physiology*
  • Male
  • Mice
  • Mice, Inbred BALB C

Substances

  • Antibodies, Monoclonal
  • Cytokines
  • Macrophage Colony-Stimulating Factor
  • Dextran Sulfate