SPONTANEOUS INTESTINAL INFLAMMATION AND NITRIC-OXIDE METABOLISM IN HLA-B27 TRANSGENIC RATS

Background & Aims: It has been reported that transgenic rats expressing the HLA-B27 and the beta(2)-microglobulin genes develop spontaneous gastrointestinal (GI) inflammation; however, no systematic or quantitative evaluation of this GI inflammation has been reported. Therefore, the objective of this study was to characterize quantitatively the GI injury and inflammation observed in commercially available HLA-B27 transgenic vats. Methods: HLA-B27 rats and Fisher 344 male controls were used for these studies. Gastric, ileal, and colonic blood-to-lumen clearances of Cr-51-ethylenediaminetetraacetic acid, tissue myeloperoxidase activities, and wet/dry ratios of the various tissues as well as plasma nitrate and nitrite levels were quantified for each control and transgenic animal. Results: Spontaneous ileitis and colitis developed in 5 of 10 HLA-B27 transgenic vats beginning at approximately 17 weeks of age and persisting for an additional 13 weeks. Increases in mucosal permeability and myeloperoxidase activities as well as histological analysis showed intestinal injury and chronic inflammation. Plasma levels of nitrate and nitrite, the stable decomposition products of nitric oxide, were found to be significantly enhanced (fourfold) only in those rats that developed the intestinal inflammation. Conclusions: The chronic ileitis and colitis observed in HLA-B27 transgenic rats seems to be associated with enhanced NO metabolism.