Trinitrobenzene sulfonic acid-induced colitis
Administration of an enema containing trinitrobenzene sulfonic acid (TNBS) results in the development of colitis in animals studied. The colitis has the features of a delayed-type hypersensitivity response to TNBS. Variations are seen in the response amongst different strains of mice, and mice could potentially be used to define genes that control susceptibility of disease. These mice have responded well to drugs used in the treatment of IBD and provide a useful model with which to study newer modalities of treatment.
Rectal irrigation of Sprague Dawley rats with 1 ml of 4% acetic acid results in epithelial injury and necrosis. The model, although lacking in chronicity, is useful for studying anti-inflammatory drugs. Mice given butyric acid also exhibit colitis, but it is not clear whether this is due to a different mechanism from acetic acid because butyric acid is a much weaker acid; butyrate itself has specific effects on intestinal epithelial cells.
Immune complex/formalin colitis
A model of colitis is seen when 0.45% unbuffered formaldehyde is inserted rectally with 0.85 ml of immune complexes injected into the car vein of New Zealand white rabbits. The distal colitis is associated with crypt distortion, abscess formation, increased production of IL-1 and leukotriene B4. Attenuation of the disease is seen when IL-1 antagonists are given, suggesting a central role for this cytokine in the disease. In addition sulfasalazine, mesalamine and azathioprine (all agents effective in treating IBD) decrease the severity of the colitis.
Dose-dependent ulceration is seen in rodents given subcutaneous injections of indomethacin. Chronic intestinal inflammation results and is associated with extra intestinal manifestations of hepatic inflammation, anemia and leukocytosis. Prostaglandins appear to be protective, while bacteria may promote the inflammatory response. Sulfasalazine, metronidazole and IL-1 antagonists attenuate the disease.
Guinea pigs given drinking water with 5% degraded carrageenan develop cecal inflammation in 5-7 days. Germ-free animals do not develop disease. The inflammation resolves with sulfasalazine and mesalamine. The model provides insights into possible interactions between endogenous bacterial flora and dietary constituents in the gut.
Cyclical administration of 5% dextran sulfate results in a chronic intestinal inflammation in Swiss Webster mice. Again IL-1 receptor antagonists will ameliorate the disease. Luminal cyclosporine is also beneficial, while metronidazole prevents colonic inflammation and dysplasia.
Lewis rats given intramural injections of peptido-glycan-polysaccharide polymers develop an enterocolitis associated with granulomatous hepatitis, arthritis and anemia. Cecal mRNA for IL-1, IL-6 and cytokine-induced neutrophil chemoattractant (CINC/GRO) are increased. Cyclosporine and steroids aid in resolution of the disease.
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