Rabbit granulomatous enterocolitis induced by injection of muramyl dipeptide emulsified with Freund's incomplete adjuvant

Abstract

We induced granulomatous enterocolitis in rabbits by injecting them with muramyl dipeptide (MDP), a subunit of the peptidoglycan polymers that endow the bacterial cell wall with structural rigidity, emulsified with Freund's incomplete adjuvant (FIA). Injections of 0.1ml of a water-in-oil emulsion of MDP and FIA were given submucosally at six sites in the rectum and colon, 10cm 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 injected six times at 1-and 2-weeks intervals, and were sacrificed 1 and 2 weeks 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 lymphocytes, granulomatous lesions, and granulomas, although the findings differed in degree. Cellular infiltration in hyperplastic villi and denuded epithelia of the small intestine were seen in 2 of 8 rabbits repeated that received MDP emulsion injections. The histological changes in this animal model may be useful for studying the pathogenesis of inflammatory bowel disease in humans.