Administration of dextran sulfate sodium (DSS) solutions to rats induced colitis which resembled mucosal lesions of human ulcerative colitis. Recent reports have shown that some cytokines are related to the pathogenesis of ulcerative colitis. In the present report, we describe the production of two cytokines in colitis mucosa in this DSS model. Using a cytotoxicity assay and a radioimmunoassay, we observed significant increases in levels of tumor necrosis factor-α (TNF-α) in the colitis mucosa and detected interleukin-1α in the mucosa of 3 of 5 DSS rats and an increase in TNF-α had a tendency to be inhibited by treatment with FK 506. Immunohistochemical investigation of DSS mucosa showed that the number of activated T cells increased at the earlier phase of inflammation. Luminol-dependent chemiluminescence values and myeloperoxidase activities were increased in the late phase of colitis and were suppressed by the FK 506 treatment. These findings may support the role of TNF-α and T-cell activation in the pathogenesis of DSS colitis.
This study was performed to clarify the relationship between activated (HLA-DR-expressing) CD4+ and CD8+ cells in the colonic lamina propria of ulcerative colitis and other immunological factors, i.e., epithelial DR expression, serum soluble CD25 levels, and colonic mucosal CD25+ cells. The frequency of epithelial DR expression was positively correlated with the numbers of CD4+ and CD8+ cells. The percentages activated CD4+/CD4+ cells were higher in mucosae with DR- epithelium than in mucosae with DR+ epithelium. The serum soluble CD25 levels were increased in ulcerative colitis, and there was an inverse correlation between these levels and the relative number of activated CD4+ cells in untreated active disease. These results suggest that interactions among mucosal CD4+ cells, colonic epithelium, and serum soluble CD25 might play an important role in the pathogenesis of ulcerative colitis.
, and the Publisher, the British Institute of Radiology, most gratefully acknowledge the contribution of the following colleagues who have acted unstintingly as referees.
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