Blockade of colony stimulating factor-1 (CSF-I) leads to inhibition of DSS-induced colitis.
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.
Marshall
Diane
D
Celltech Centre of Excellence for Antibody Research, UCB, 216 Bath Road, Slough SLI 4EN, UK. diane.marshall@celltech.ucb-group.com
Cameron
James
J
Lightwood
Daniel
D
Lawson
Alastair D G
AD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002465:Cell Movement; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D066298:In Vitro Techniques; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D016207:Cytokines; D016173:Macrophage Colony-Stimulating Factor; D016264:Dextran Sulfate