HDL biology
A review names LCAT, hepatic lipase, and CETP as the key HDL-remodeling enzymes suppressed during cytokine-driven hyperlipidemia (Z Ernahrungswiss 1998)
Original title: Beneficial effects of cytokine induced hyperlipidemia
This review discusses how infection, inflammation, and trauma trigger a cytokine-mediated acute phase response that alters lipid metabolism and circulating lipoprotein levels. Cytokines including TNF, interleukins, and interferons rapidly raise serum triglycerides mainly via increased hepatic VLDL secretion, and in non-primate animals also raise serum cholesterol by increasing hepatic cholesterol synthesis while decreasing cholesterol catabolism. Injury and cytokines also lower HDL cholesterol and alter HDL composition, increasing serum amyloid A and apolipoprotein J content while apolipoprotein A1 may decrease and free cholesterol rises relative to cholesterol ester. Key HDL-remodeling enzymes are also altered: LCAT activity, hepatic lipase activity, and CETP levels all decrease. The authors propose these lipid changes form part of a beneficial innate immune response, aiding functions such as pathogen neutralization and nutrient redistribution for immune and repair processes.
Original abstract
Infection, inflammation and trauma induce marked changes in the plasma levels of a wide variety of proteins (acute phase response), and these changes are mediated by cytokines. The acute phase response is thought to be beneficial to the host. The host's response to injury also results in dramatic alterations in lipid metabolism and circulating lipoprotein levels which are mediated by cytokines. A large number of cytokines including TNF, the interleukins, and the interferons increase serum triglyceride levels. This rapid increase (1-2 h) is predominantly due to an increase in hepatic VLDL secretion while the late increase may be due to a variety of factors including increased hepatic production of VLDL or delayed clearance secondary to a decrease in lipoprotein lipase activity and/or apolipoprotein E levels on VLDL. In animals other than primates, cytokines also increase serum cholesterol levels, most likely by increasing hepatic cholesterol. Cytokines increase hepatic cholesterol synthesis by stimulating HMG CoA reductase gene expression and decrease hepatic cholesterol catabolism by inhibiting cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis. Injury and/or cytokines also decrease HDL cholesterol levels and induce alterations in the composition of HDL. The content of SAA and apolipoprotein J increase, apolipoprotein A1 may decrease, and the cholesterol ester content decreases while free cholesterol increases. Additionally, key proteins involved in HDL metabolism are altered by cytokines; LCAT activity, hepatic lipase activity, and CETP levels decrease. These changes in lipid and lipoprotein metabolism may be beneficial in a number of ways including: lipoproteins competing with viruses for cellular receptors, apolipoproteins neutralizing viruses, lipoproteins binding and targeting parasites for destruction, apolipoproteins lysing parasites, redistribution of nutrients to cells involved in the immune response and/or tissue repair, and lipoproteins binding toxic agents and neutralizing their harmful effects. Thus, cytokines induce marked changes in lipid metabolism that lead to hyperlipidemia which represents part of the innate immune response and may be beneficial to the host.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.