PT  - JOURNAL ARTICLE
AU  - Hitoshi Ando
AU  - Toshinari Takamura
AU  - Tsuguhito Ota
AU  - Yukihiro Nagai
AU  - Ken-ichi Kobayashi
TI  - Cerivastatin Improves Survival of Mice with Lipopolysaccharide-Induced Sepsis
DP  - 2000 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1043--1046
VI  - 294
IP  - 3
4099  - http://jpet.aspetjournals.org/content/294/3/1043.short
4100  - http://jpet.aspetjournals.org/content/294/3/1043.full
SO  - J Pharmacol Exp Ther2000 Sep 01; 294
AB  - Development of severe sepsis is thought to result from the overproduction of cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and nitric oxide. Recently, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, which are antihypercholesterolemic agents, have been reported to inhibit lipopolysaccharide (LPS)-induced production of cytokines and nitric oxide in vitro. In this study, we tested these effects in vivo. After LPS administration (15 mg/kg i.p.) to CD-1 mice, serum levels of both TNF-α and IL-1β transiently increased, and peaked at 2 h. After the peak responses of TNF-α and IL-1β, serum levels of nitrite and nitrate increased until at least 8 h. Pretreatment of the mice with cerivastatin (20 mg/kg i.p. 12 and 1 h before LPS injection) reduced serum levels of TNF-α and IL-1β at 2 h, and nitrite and nitrate at 8 h, by 93, 60, and 44%, respectively. In this model of sepsis, cerivastatin significantly (P= .016) improved the rate of 7-day survival from 26.7 to 73.3%. These results cast new light on the usefulness of cerivastatin in preventing severe sepsis. The American Society for Pharmacology and Experimental Therapeutics