Experimental colitis increases small intestine permeability in the rat

Small intestine permeability is frequently altered in patients with Crohn's disease and is thought to play a pathogenic role. The aim of this study wa s to investigate the permeability and structure of small intestine tight ju nctions (TJ) in an animal model of chronic distal colitis. Seven days after colitis induction with trinitrobenzenesulfonic acid/ethanol, the duodenal and ileal TJ were studied by means of transmission electron microscopy usin g lanthanum nitrate, freeze fractures, and immunohistochemistry of occludin , ZO-1, and cingulin. Animals treated with intrarectal ethanol alone served as controls. in controls, 7.5% of duodenal and 9.6% of ileal TJ were perme able to lanthanum, whereas in colitis, permeability increased significantly (79.5% and 72.9%, respectively; p < 0.001, both segments compared with con trols). In colitis, the percentage of "leaky" junctions in duodena as well as in terminal ilea correlated positively with the macroscopic colon damage score (p < 0.02 and p < 0.005, respectively). Freeze-fracture analysis and immunohistochemistry of cingulin and ZO-1 did not reveal any difference be tween control and treated animals, whereas the signal of the transmembrane protein occludin was found to be disrupted and irregular in both small inte stine segments. Distal colitis induces an increase of TJ permeability throu ghout the entire small intestine, and the extent of alterations correlates with colonic damage. Alterations in the transmembrane protein occludin seem to be responsible for the observed changes. Further investigation is neede d to elucidate the mechanism of TJ alterations by a remote focus of inflamm ation.