Shuichi Yotsuya*, Hiroshi Shikama and Masashi Imamura
Central Research Institute, Ishihara Sangyo Kaisha, Ltd., 2-3-1, Nishi-Shibukawa, Kusatsu, Shiga 525-0025, Japan
*Corresponding author. FAX: +81-77-562-9783, E-mail: s-yotsuya@iskweb.co.jp
Abstract: We examined the therapeutic effects of the inflammatory cell infiltration inhibitor IS-741 (N-(2-((ethylsulfonyl)amino)-5-(trifluoromethyl)-3-pyridinyl)-cyclohexanecarboxamide monosodium salt monohydrate) on a rat colitis model. As a result of its effects on leukocyte infiltration, IS-741 inhibits cell adhesion, alleviates symptoms and signs of pancreatitis and multiple organ failure and demonstrates a life-saving effect in a model of severe acute pancreatitis. A rat model was prepared by inducing colitis with 3% dextran sodium sulfate (DSS) and maintaining pathology with 1% DSS. Repeated oral administration of IS-741 at 1, 10 or 100 mg/kg per day was conducted for 2 weeks (during treatment with 1% DSS). IS-741 at each dose decreased the area of erosion in the large intestine, thickening of the wall of the large intestine and anemia caused by melena. Some effects of IS-741 were nearly equivalent to those of the control compound salazosulfapyridine. Furthermore, IS-741 markedly alleviated inflammatory cell infiltration into the intestinal wall. IS-741 improved lesions in a rat DSS model by inhibiting leukocyte infiltration, suggesting the possibility of clinical application of this drug for IBD.
Keywords: IS-741, Inhibition of cell adhesion, Inhibition of leukocyte infiltration, Inflammatory bowel disease, Ulcerative colitis
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