Colonic inflammation in the rabbit induced by phorbol-12-myristate-13-acetate.
Neutrophil (PMNL) infiltration of inflamed colonic tissue is a prominent feature of human inflammatory bowel disease (IBD). Colitis was established in New Zealand white rabbits by the intrarectal instillation of 1.5 mg/kg (in 10 ml 20% ethanol) phorbol-12-myristate-13-acetate (PMA) and assessed by visual grading of colonic inflammation, levels of the neutrophil marker enzyme myeloperoxidase (MPO), and histological examination. After 24 h there was a significant (P less than 0.001) increase in MPO levels in the PMA-treated colons compared to ethanol control. There was also increased inflammation based on visual scoring. Histologically, PMA-treated colons were necrotic with focal ulceration, heavy PMNL infiltration and edema at 24 h; by 96 h colitis was sustained with mild edema, crypt abscesses, and a staining pattern suggesting altered mucus quality. These results suggest that PMA-induced colitis in rabbits may be a new model of IBD in which to evaluate drugs known to mitigate the inflammatory process.
Fretland
D J
DJ
Department of Gastrointestinal Diseases Research, G. D. Searle and Co., Skokie, Illinois 60077.
Widomski
D L
DL
Levin
S
S
Gaginella
T S
TS
D000818:Animals; D004796:Clinical Enzyme Tests; D003092:Colitis / Q000139:chemically induced* / Q000175:diagnosis; D003106:Colon / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D009195:Peroxidase / Q000032:analysis; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate