Funded by National Institutes of Health (NIH) grant K08DK080172-01 (to P.D.R.H.) and a grant from the University of Michigan Peptide Center.
Intestinal fibrosis is reduced by early elimination of inflammation in a mouse model of IBD: Impact of a “Top-Down” approach to intestinal fibrosis in mice†
Article first published online: 14 JUL 2011
Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 3, pages 460–471, March 2012
How to Cite
Johnson, L. A., Luke, A., Sauder, K., Moons, D. S., Horowitz, J. C. and Higgins, P. D.R. (2012), Intestinal fibrosis is reduced by early elimination of inflammation in a mouse model of IBD: Impact of a “Top-Down” approach to intestinal fibrosis in mice. Inflamm Bowel Dis, 18: 460–471. doi: 10.1002/ibd.21812
- Issue published online: 13 FEB 2012
- Article first published online: 14 JUL 2011
- Manuscript Accepted: 2 JUN 2011
- Manuscript Received: 25 MAY 2011
- Crohn's disease;
- intestinal fibrosis;
- top-down interventional approach;
- Salmonella typhimurium
The natural history of Crohn's disease follows a path of progression from an inflammatory to a fibrostenosing disease, with most patients requiring surgical resection of fibrotic strictures. Potent antiinflammatory therapies reduce inflammation but do not appear to alter the natural history of intestinal fibrosis. The aim of this study was to determine the relationship between intestinal inflammation and fibrogenesis and the impact of a very early “top-down” interventional approach on fibrosis in vivo.
In this study we removed the inflammatory stimulus from the Salmonella typhimurium mouse model of intestinal fibrosis by eradicating the S. typhimurium infection with levofloxacin at sequential timepoints during the infection. We evaluated the effect of this elimination of the inflammatory stimulus on the natural history of inflammation and fibrosis as determined by gross pathology, histopathology, mRNA expression, and protein expression.
Fibrogenesis is preceded by inflammation. Delayed eradication of the inflammatory stimulus by antibiotic treatment represses inflammation without preventing fibrosis. Early intervention significantly ameliorates but does not completely prevent subsequent fibrosis.
This study demonstrates that intestinal fibrosis develops despite removal of an inflammatory stimulus and elimination of inflammation. Early intervention ameliorates but does not abolish subsequent fibrosis, suggesting that fibrosis, once initiated, is self-propagating, suggesting that a very early top-down interventional approach may have the most impact on fibrostenosing disease. (Inflamm Bowel Dis 2012;)