title: Simvastatin treatment improves survival in a murine model of burn sepsis: Role of interleukin 6.
abstract: Infection is the most common and most serious complication of a major burn related to burn size. Recent studies have demonstrated that statin treatment can decrease mortality in murine or human sepsis. In the current study mice were anesthetized and subjected to a dorsal 30% TBSA scald burn. Simvastatin or placebo were administered by intraperitoneal injection once daily or every 12h. On post burn day 7 cecal ligation and puncture with a 21-gauge needle (CLP) was performed under ketamine/xylazine anesthesia, the two different dosing schedules were continued and survival was monitored. In other groups of mice, interleukin-6 (IL-6) levels in blood were measured in mice at 7 days after injury. A simvastatin dependent improvement in survival was observed in the burn sepsis model. This protection was found to be dose and time dependent. In addition, statin treatment reduced the elevation in IL-6 levels of mice burned 7 days previously. However, IL-6 levels in burned mice with or without statin treatment were elevated by CLP to the same degree. The results of these studies suggest that statin treatment reduces mortality in mice with burns and CLP and that this effect may not be mediated via IL-6 levels.
authors.affiliation: Surgical Service, Massachusetts General Hospital, Shriners Hospitals for Children, and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Beffa
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Fischman
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Fagan
authors.forename: Victoria F
authors.initials: VF
authors.lastname: Hamrahi
authors.forename: Kasie W
authors.initials: KW
authors.lastname: Paul
authors.forename: Masao
authors.initials: M
authors.lastname: Kaneki
authors.forename: Yong-Ming
authors.initials: YM
authors.lastname: Yu
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.forename: Edward A
authors.initials: EA
authors.lastname: Carter
mesh_terms: D000818:Animals; D002056:Burns / Q000150:complications / Q000378:metabolism* / Q000401:mortality; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D051379:Mice; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D019821:Simvastatin / Q000627:therapeutic use*; D016019:Survival Analysis
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D019821:Simvastatin