Simvastatin attenuates trinitrobenzene sulfonic acid-induced colitis, but not oxazalone-induced colitis.
OBJECTIVE
To determine whether simvastatin is able to inhibit inflammation in trinitrobenzene sulfonic acid (TNBS)-induced or oxazalone (OXA)-induced colitis.


RESULTS
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.


CONCLUSIONS
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.
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Maho
M
Ikeda
Fuminao
F
Takeshima
Hajime
H
Isomoto
Saburo
S
Shikuwa
Yohei
Y
Mizuta
Yoshiyuki
Y
Ozono
Shigeru
S
Kohno
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010081:Oxazolone / Q000633:toxicity; D019821:Simvastatin / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010081:Oxazolone; D014302:Trinitrobenzenesulfonic Acid; D019821:Simvastatin