Protein Limits Fibrosis in Inflammatory Bowel Disease

Process may reduce bowel obstructions and surgeries.

A new treatment utilizing a natural protein may decrease the number of surgeries needed by patients with inflammatory bowel disease (IBD), the results of a recent study found.

Published in the inaugural issue of Cellular and Molecular Gastroenterology and Hepatology, the study examines a treatment for fibrosing strictures that obstruct the intestines and cause a major complication for Crohn's disease patients. While the obstructions are typically removed through surgery, disease recurrence at those sites is typical, which subjects patients to numerous surgeries throughout their lives.

"We found that the antimicrobial defense protein cathelicidin can prevent such intestinal fibrosis in pre-clinical disease models," senior author Hon Wai Koon, PhD, said in a press release. "These findings may lead to novel therapeutic approaches that prevent recurrent strictures in Crohn's disease patients."

The study evaluated the use of cathelicidin, which is part of a family of antimicrobial proteins produced by numerous cell types, including acute and chronic inflammatory and epithelial cells. The protein was previously found to carry anti-inflammatory properties that suppress collagen synthesis, which is the core protein of fibrotic scars.

In the current study, researchers examined whether cathelicidin can prevent collagen synthesis and fibrosis in intestinal disease, which could reduce strictures that frequently cause bowel obstructions and multiple surgical resections. As a result of these strictures, patients are left with so little bowel that nutrients have to be provided intravenously because they are not adequately absorbed from food.

In a mouse model of Crohn's disease that induced chronic colitis and fibrosis over 7 weeks, instilling cathelicidin through the colon over the final 3 weeks limited weight loss and microscopic disease features, in addition to reducing production of tumor necrosis factor-α. The therapy also reduced microscopic evidence of fibrosis and production of mRNA for synthesis of collagen.

The expression of transforming growth factor-α, which carries anti-inflammatory and pro-regenerative properties, was not affected by the treatment.

"While the precise mechanisms by which cathelicidin promotes healing and inhibits fibrosis remain an area of future study, the advances described in this study may make it possible to prevent recurrent strictures and spare these patients from repeated surgery," said Jerrold Turner, MD, PhD, AGAF, in a press release.