HDL biology
CETP discovered to protect mice against lethal bacterial endotoxin by dampening the inflammatory response (Shock 2008)
Original title: Human cholesteryl ester transfer protein expression enhances the mouse survival rate in an experimental systemic inflammation model: a novel role for CETP
Mice expressing human CETP proved more resistant to E. coli lipopolysaccharide (LPS): all huCETP+/+ mice survived five days after intraperitoneal LPS inoculation, while more wild-type mice died, and huCETP+/+ mice showed smaller rises in plasma TNF-alpha and IL-6. LPS elicited lower TNF-alpha production from CETP-expressing than wild-type macrophages, and adding human CETP to RAW 264.7 macrophages dose-dependently reduced their LPS-induced TNF-alpha output. Human CETP also enhanced LPS binding to plasma HDL/LDL in vitro and increased hepatic uptake of infused Salmonella typhimurium LPS in huCETP+/+ mice. This is the first evidence that CETP is an endogenous component of the first-line defense against excessive proinflammatory mediator production during bacterial endotoxemia.
Original abstract
Mice expressing human cholesteryl ester transfer protein (huCETP) are more resistant to Escherichia coli bacterial wall LPS because death rates 5 days after intraperitoneal inoculation of LPS were higher in wild-type than in huCETP+/+ mice, whereas all huCETP+/+ mice remained alive. After LPS inoculation, plasma concentrations of TNF-alpha and IL-6 increased less in huCETP+/+ than in wild-type mice. LPS in vitro elicited lower TNF-alpha production by CETP expressing than by wild-type macrophages. In addition, TNF-alpha production by RAW 264.7 murine macrophages increased on incubation with LPS but decreased in a dose-dependent manner when human CETP was added to the medium. Human CETP in vitro enhanced the LPS binding to plasma high-density lipoprotein/low-density lipoprotein. The liver uptake of intravenous infused 14C-LPS from Salmonella typhimurium was greater in huCETP+/+ than in wild-type mice. Present data indicate for the first time that CETP is an endogenous component involved in the first line of defense against an exacerbated production of proinflammatory mediators.
HDL biologyinfectionmechanisms
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.