Ikeda Maho, Takeshima Fuminao, Isomoto Hajime, Shikuwa Saburo, Mizuta Yohei, Ozono Yoshiyuki, Kohno Shigeru
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Dig Dis Sci. 2008 Jul;53(7):1869-75. doi: 10.1007/s10620-007-0102-0. Epub 2007 Dec 1.
To determine whether simvastatin is able to inhibit inflammation in trinitrobenzene sulfonic acid (TNBS)-induced or oxazalone (OXA)-induced colitis.
In the prophylactic protocol, simvastatin dose-dependently suppressed the decrease in body weight and inflammatory grade of TNBS-treated mice. In contrast, in the therapeutic protocol, no significant difference in body weight reduction was observed between simvastatin-treated and control mice. IFN-gamma release from LP cells was significantly suppressed in mice receiving high-dose simvastatin in the prophylactic protocol. In contrast to TNBS colitis, even high-dose prophylactic simvastatin had no suppressive effects on either weight reduction or the inflammatory grade in OXA colitis.
Our results indicate that simvastatin negatively regulates inflammation in TNBS-induced colitis, but not in OXA-induced colitis. In TNBS-induced colitis, simvastatin suppressed the Th1-polarized immune response. Our findings suggest that simvastatin has potential effects as a therapeutic agent in human inflammatory bowel disease, particularly Crohn's disease.