Understanding changes in high density lipoproteins during the acute phase response.

During infection and inflammation there is a cascade of reactions that occurs in the host collectively known as the acute-phase response (APR).1 Besides alterations in acute-phase reactants (plasma proteins), the APR is also associated with changes in lipoproteins.2 Increasing evidence suggests that high density lipoproteins (HDL) are a critical part of the acute phase response (APR) of the innate immune system.3 During infection and inflammation, there is a reduction in levels of several plasma proteins involved in HDL-mediated reverse cholesterol transport and inhibiting plasma lipid oxidation, such as lecithin:cholesterol acyltransferase (LCAT), cholesterol ester transfer protein, phospholipid transfer protein, hepatic lipase, apolipoprotein A-I (apoA-I), and paraoxonase (PON).2 Moreover, the composition of circulating HDL during an APR, also known as acute-phase HDL, is altered. Analysis of the lipid composition shows that acute-phase HDL is depleted in cholesterol ester but enriched in free cholesterol, triglyceride, and free tty acids.4 Changes in the phospholipid content of acute-phase HDL was shown to be more variable, having increased in one study5 but decreased in another.6 The levels of apolipoprotein J (apoJ or clusterin) and serum amyloid A (SAA) increase several fold in acute-phase HDL.7 Because of the marked changes in HDL during an APR, acute-phase HDL behaves differently from normal HDL in terms of its protective effect against atherosclerosis.8 Malle and coworkers have shown that acute-phase HDL was less effective in removing cholesterol from macrophages.9 Delivery of cholesterol ester to hepatocytes is also decreased during an APR because of changes in HDL composition and a reduction in hepatic scavenger receptor class B type.10