RABBIT GRANULOMATOUS ENTEROCOLITIS INDUCED BY INJECTION OF MURAMYL DIPEPTIDE EMULSIFIED WITH FREUNDS INCOMPLETE ADJUVANT

We induced granulomatous enterocolitis in rabbits by injecting them wi th muramyl dipeptide (MDP), a subunit of the peptidoglycan polymers th at endow the bacterial cell wall with structural rigidity, emulsified with Freund's incomplete adjuvant (FIA). Injections of 0.1 ml of a wat er-in-oil emulsion of MDP and FIA were given submucosally at six sites in the rectum and colon, 10 cm proximal to the anus, using a flexible endoscope. Four rabbits each were sacrificed 1, 2, and 4 weeks after a single injection of the emulsion. Another 4 rabbits each were inject ed six times at 1- and 2-week intervals, and were sacrificed 1 and 2 w eeks after the last injection of the emulsion, respectively. In all 20 rabbits, injected with the MDP emulsion, histological findings of the colon consisted of cellular infiltrations of plasma cells and lymphoc ytes, granulomatous lesions, and granulomas, although the findings dif fered in degree. Cellular infiltration in hyperplastic villi and denud ed epithelia of the small intestine were seen in 2 of 8 rabbits repeat ed that received MDP emulsion injections. The histological changes in this animal model may be useful for studying the pathogenesis of infla mmatory bowel disease in humans.