Endotoxin-induced mortality in bile duct—ligated rats after administration of reconstituted high-density lipoprotein

Abstract Cholestatic patients have substantial morbidity because of increased susceptibility to endotoxin (lipopolysaccharide [LPS]). Although reconstituted high-density lipoprotein (rHDL) can bind and neutralize LPS, cholestasis is associated with a near complete absence of HDL. Effects of rHDL infusion on the outcome of LPS-induced inflammatory responses in cholestatic rats were determined. Bile duct-ligated (BDL) and sham rats were treated with rHDL or saline and challenged with LPS. Distribution of cholesterol over the lipoprotein subclasses changed by ligation: levels in low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) were increased 2-fold and 5-fold, respectively, and were decreased in HDL 2-fold. rHDL treatment did not affect cholesterol distribution. LPS was mainly found in the HDL fraction, and ligation affected only levels of HDL-bound LPS (50% decrease; P P P