Inflammatory bowel disease induced by combined bacterial immunization and oral carrageenan in guinea pigs. Model development, histopathology, and effects of sulfasalazine.
A model of experimentally induced inflammatory bowel disease (IBD) featuring colitis, originally devised by Onderdonk and co-workers in guinea pigs, was modified to establish the optimal conditions for ulcer development. Upon varying the time of subcutaneous immunization with Bacteroides vulgatus and concomitant oral administration of acid-degraded iota-carrageenan and viable B. vulgatus, it was found that the optimal times of administering these agents were one to two weeks and five to six days, respectively. Light microscopy of the colon and cecum of the guinea pigs given the optimized treatment for ulcer induction revealed pronounced edema, inflammation, and lesions of the mucosa. Transmission electron microscopy of the mucosa from these animals showed the presence of large numbers of leukocytes in the subepithelial region, the majority being polymorphonuclear neutrophils which possessed large electron-dense granules or rods. Oral administration of 300 mg/kg/day sulfasalazine (salicylazosulfapyridine) for 14 days to guinea pigs given the optimized treatment for ulcer induction failed to reduce the numbers of ulcers or the histopathology gradings and fine structural changes of the mucosal inflammatory changes, but did reduce the symptoms of diarrhea.
Oestreicher
P
P
Department of Experimental Therapeutics, Wyeth Laboratories Inc., Philadelphia, Pennsylvania.
Nielsen
S T
ST
Rainsford
K D
KD
D000818:Animals; D001439:Bacteroides / Q000276:immunology; D002351:Carrageenan; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000648:ultrastructure; D006168:Guinea Pigs; D007114:Immunization; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D007962:Leukocytes / Q000648:ultrastructure; D008297:Male; D008855:Microscopy, Electron, Scanning; D009504:Neutrophils / Q000648:ultrastructure; D012460:Sulfasalazine / Q000627:therapeutic use
D012460:Sulfasalazine; D002351:Carrageenan