Endotoxin and interleukin-1 decrease hepatic lipase mRNA levels

The acute phase response induces a multitude of changes in lipoprotein meta bolism including hypertriglyceridemia, triglyceride enriched LDL, and decre ased HDL levels accompanied by changes in HDL composition including increas ed free cholesterol and triglycerides and a decrease in esterified choleste rol. Here we demonstrate that endotoxin (LPS) induces a 56% decrease in hep atic lipase activity in liver and a 45% decrease in hepatic lipase activity in post heparin plasma in Syrian hamsters. LPS treatment also produces a m arked decrease in hepatic lipase mRNA levels in the liver. Half maximal red uction in hepatic lipase mRNA levels occurred at approximate to 0.2 mu g LP S/100 g BW with a maximal decrease at 1.0 mu g/100 g BW (> 90% decrease), i ndicating that inhibition of hepatic lipase is a sensitive host response to LPS. Additionally, IL-1 produced a marked decrease in hepatic lipase mRNA levels while TNF had no effect. Moreover, IL-1 treatment of HepG2 cells in vitro also decreased hepatic lipase mRNA levels suggesting that IL-1 can di rectly regulate hepatic lipase expression in liver cells. LPS decreased hep atic lipase mRNA levels in control as well as IL-I type 1 receptor deficien t mice indicating that IL-1 action is not absolutely essential and that sev eral cytokines and/or small molecular mediators can regulate hepatic lipase during the acute phase response. The LPS and IL-1 induced decrease in hepa tic lipase could have several consequences including decreasing the clearan ce of triglyceride rich lipoprotein particles and producing an increase in triglyceride rich HDL. The decrease in hepatic lipase activity and mRNA lev els may be part of a series of coordinated changes in lipoprotein metabolis m that occur during the acute phase response. These changes may be initiall y beneficial to the host but if present for an extended period may be proat herogenic. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.