rss
Gut 44:636-642 doi:10.1136/gut.44.5.636
  • Inflammation and inflammatory bowel disease

Trefoil peptide TFF2 (spasmolytic polypeptide) potently accelerates healing and reduces inflammation in a rat model of colitis

  1. C P Trana,
  2. G A Cooka,
  3. N D Yeomansa,
  4. L Thimb,
  5. A S Girauda
  1. aUniversity of Melbourne, Australia, bNovo Nordisk, Bagsvaerd, Denmark
  1. Associate Professor A S Giraud, University of Melbourne, Department of Medicine at Western Hospital, Footscray 3011, Australia. email:ag{at}medicine.unimelb.edu.au
  • Accepted 17 December 1998

Abstract

BACKGROUND The trefoil peptides are major secretory products of mucus cells of the gastrointestinal tract and show increased expression after inflammatory or ulcerative damage. Recombinant human TFF2 (spasmolytic polypeptide) has been shown to be cytoprotective, and enhances repair in models of gastric injury.

AIMS To test the healing effects of recombinant human (h)TFF2 in a rat model of chronic colitis.

METHODS Colitis was induced by intracolonic administration of dinitrobenzene sulphonic acid in ethanol. Mucosal repair was quantified macroscopically, microscopically by image analysis of tissue histology, and by measuring myeloperoxidase activity.

RESULTS Initial validation studies showed that maximal injury and inflammation occurred at the end of the first week after colitis induction (active phase), and that spontaneous healing was complete by eight weeks. Once daily intrarectal application of hTFF2 (2.5 mg/kg; approximately 0.5 mg/rat) for five days after maximal damage had been sustained, reduced both microscopic and macroscopic injury by 80% and inflammatory index by 50% compared with vehicle controls. In addition, endogenous concentrations of rat TFF2 and TFF3 (intestinal trefoil factor) were increased in the active phase of colitis and were reduced to basal levels by hTFF2 treatment.

CONCLUSIONS This study has shown that hTFF2 enhances the rate of colonic epithelial repair, and reduces local inflammation in a rat model of colitis, and suggests that luminal application of trefoil peptides may have therapeutic potential in the treatment of inflammatory bowel disease.

Footnotes

  • Abbreviations:
    MPO
    myeloperoxidase
    TFF2
    spasmolytic polypeptide
    TFF3
    intestinal trefoil factor
    IBD
    inflammatory bowel disease
    SP
    spasmolytic peptide
    ITF
    intestinal trefoil factor
    DNBS
    dinitrobenzenesulphonic acid
    MC
    carboxymethylcellulose
    MPO
    myeloperoxidase
    HTAB
    hexadecyl trimethylammonium bromide
    TGF
    transforming growth factor