Effects of lambda-carrageenan induced experimental enterocolitis on splenocyte function and nitric oxide production

A lambda-carrageenan induced rat model of inflammatory bowel disease (IBD) allowed evaluation of progressive histopathological changes over time and comparison with human disease. In addition, this model was used to test the hypothesis that the immunosuppression observed in IBD may be mediated in part by augmented production of nitric oxide by splenic lymphocytes. Male Sprague-Dawley rats were fed standard rat chow and a drinking solution of 2% lambda-carrageenan without prior sensitization to the compound. At 2, 4, 6, and 8 weeks, small and large intestines were removed for histological examination, and splenocytes were assayed for response to various mitogens and for nitrite production. Intestinal lesions gradually developed in lambda-carrageenan fed rats and were found to be morphologically similar to those observed in human ulcerative colitis. The proliferative response of splenocytes to known mitogens was significantly diminished in carrageenan fed rats, when compared with pair-fed controls, but was fully restored when cultured in the presence of NG-monomethyl-L-arginine, a specific inhibitor of nitric oxide synthase. Preliminary data suggest that overproduction of nitric oxide may provide a molecular mechanism for the immunosuppression observed during chronic inflammatory bowel disease. Further characterization of a reproducible rat model of IBD will allow further investigation into the pathogenesis of the human disease.