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The Korean Journal of Pathology 2004;38(6): 401-407.
Effect of Atorvastatin, a HMG-CoA Reductase Inhibitor, in Experimental Colitis in Mice.
Hyo Jin Park, Tae Woon Kim, Jae Nam Seo, Kwon Ik Oh, Eun Young Choi, Hyung Sik Shin, Young Euy Park
1Department of Pathology, Hallym University College of Medicine, Chuncheon, Korea. hsshin@hallym.or.kr
2Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
3Center for Animal Resource Development, Seoul National University College of Medicine, Seoul, Korea.
ABSTRACT
BACKGROUND: The statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are approved for cholesterol reduction, and may also be beneficial in the treatment of inflammatory disease. In this study, atorvastatin was tested in experimental colitis, a disease model of inflammatory bowel disease. METHODS: To induce colitis, dextran sodium sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS) were administrated to C57BL/6 or BALB/c mice. Mice were monitored daily for loss of body weight and survival for indicated days. Colon length and histology were examined after sacrifice. RESULTS: The administration of DSS induced marked colonic inflammation and shortening, and resulted in a loss of body weight. DSSinduced colitis was not affected by atorvastatin treatment, but in contrast, the administration of atorvastatin relieved TNBS-induced colitis with a resultant rapid recovery of weight loss and a reduction in colonic length shortening. Histologically, inflammatory cell infiltration in the colonic wall, mucosal ulceration and crypt disruption were also suppressed in atorvastatin treated mice. CONCLUSION: These results suggest that atorvastatin preserves intestinal integrity in colitis, probably via the modulation of Th cell-mediated immune response, in a manner independent of innate immunity.
Key Words: Atorvastatin; Inflammatory bowel disease; Experimental colitis; Th cell mediated immunity; Immunity, Natural
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