BACKGROUND: A novel anti-inflammatory drug, IS-741, blocked the adhesion of inflammatory cells to microvascular endothelial cells both in vivo and in vitro. Transgenic rats expressing human leukocyte antigen (HLA)-B27 and human beta2-microglobulin (HLA-B27 rats) spontaneously develop chronic colitis, which resembles human inflammatory bowel disease. In the present study, the authors examined the efficacy of IS-741 against spontaneous colitis in HLA-B27 rats. METHODS: The HLA-B 27 rats were divided in two groups after the development of colitis. IS-741 was dissolved in water and administered orally (10 mg/kg) once per day for 14 days. RESULTS: The HLA-B27 rats treated with IS-741 remained healthy; the wet weight of the colon was significantly lower in the IS-741-treated group. Histological examinations revealed a marked infiltration of inflammatory cells into both the mucosa and the submucosa in the control HLA-B27 rats, but these changes were attenuated in the IS-741-treated group. The mucosal damage score was also significantly reduced by treatment with IS-741. IS-741 significantly reduced the mucosal myeloperoxidase activity and mucosal cytokine-induced neutrophil chemoattractant-1 levels. IS-741 also reduced CD3-positive T-cell infiltration. CONCLUSION: IS-741 suppressed the spontaneous colitis that developed in HLA-B27 rats. Some of the actions of IS-741 may be associated with its inhibitory effects on the adhesion of neutrophils to endothelial cells. The findings from the present study suggest that IS-741 may be a useful new therapeutic agent for inflammatory bowel disease.
BACKGROUND: A novel anti-inflammatory drug, IS-741, blocked the adhesion of inflammatory cells to microvascular endothelial cells both in vivo and in vitro. Transgenic rats expressing human leukocyte antigen (HLA)-B27 and humanbeta2-microglobulin (HLA-B27rats) spontaneously develop chronic colitis, which resembles humaninflammatory bowel disease. In the present study, the authors examined the efficacy of IS-741 against spontaneous colitis in HLA-B27rats. METHODS: The HLA-B 27 rats were divided in two groups after the development of colitis. IS-741 was dissolved in water and administered orally (10 mg/kg) once per day for 14 days. RESULTS: The HLA-B27rats treated with IS-741 remained healthy; the wet weight of the colon was significantly lower in the IS-741-treated group. Histological examinations revealed a marked infiltration of inflammatory cells into both the mucosa and the submucosa in the control HLA-B27rats, but these changes were attenuated in the IS-741-treated group. The mucosal damage score was also significantly reduced by treatment with IS-741. IS-741 significantly reduced the mucosal myeloperoxidase activity and mucosal cytokine-induced neutrophil chemoattractant-1 levels. IS-741 also reduced CD3-positive T-cell infiltration. CONCLUSION:IS-741 suppressed the spontaneous colitis that developed in HLA-B27rats. Some of the actions of IS-741 may be associated with its inhibitory effects on the adhesion of neutrophils to endothelial cells. The findings from the present study suggest that IS-741 may be a useful new therapeutic agent for inflammatory bowel disease.