Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice.

Abstract

Endotoxemia stimulates many physiologic responses including disturbances in lipid metabolism. We hypothesized that this lipemia may be part of a defensive mechanism by which the body combats the toxic effects of circulating endotoxin. We tested the effects of mixtures of endotoxin, lipoproteins, and lipoprotein-free plasma and determined the ability of varying concentrations of human very low density lipoproteins (VLDL) and chylomicrons, as well as low density lipoproteins (LDL) and high density lipoproteins (HDL), and of the synthetic lipid emulsion SOYACAL to prevent endotoxin-induced death in mice. This study demonstrates that the triglyceride-rich VLDL and chylomicrons, as well as cholesterol-rich LDL and HDL, and cholesterol-free SOYACAL can protect against endotoxin-induced death. Protection required small amounts of lipoprotein-free plasma, and depended on the incubation time and the concentration of lipoprotein lipid. Despite stringent techniques to prevent exogenous endotoxin contamination eight of ten duplicate VLDL preparations contained endotoxin (5,755±3,514 ng endotoxin/mg triglyceride, mean±SEM) making the isolation of endotoxin-free VLDL difficult. In contrast, simultaneous preparations of LDL and HDL were relatively free of endotoxin contamination (3±3 and 320±319 ng/mg total cholesterol, respectively), suggesting that the contamination of VLDL occurs in vivo and not during the isolation procedure. These observations suggest a possible role for increased triglyceride-rich lipoproteins in the host's defense against endotoxemia and infection. (J. Clin. Invest. 1990.

The Impact of Antihypertensive Drug Therapy on Endotoxemia in Elderly Patients with Chronic Kidney Disease

“…Clearance of endotoxin is affected both by humoral inactivation and through uptake into liver and mononuclear phagocyte cells (17)(18)(19)(20), and is influenced by both host and LPS-specific factors (23,24). There is a complex relationship among binding of endotoxin to antibodies, to platelets, and to lipoproteins in the modulation of its biologic effects and clearance (23,24). Endotoxemia has been initially recognized in severe decompensated heart failure (4).…”

Endotoxin and cytokines decrease serum levels and extra hepatic protein and mRNA levels of cholesteryl ester transfer protein in syrian hamsters.

“…In addition to the decrease in CETP levels, a decrease in hepatic lipase activity (7-10) may also serve to maintain HDL cholesterol levels by decreasing formation of remnant HDL 2 and thus decreasing clearance of HDL. Preserving HDL cholesterol levels during infection and inflammation may be important because of the ability of HDL to prevent the toxic effects of endotoxin (41)(42)(43) and reduce oxidative stress (44,45). Maintaining HDL cholesterol levels may also be important for delivery of cholesterol to peripheral tissues that may have increased needs for cholesterol during infection and inflammation.…”

The Association Between Cholesterol and Mortality in Heart Failure Comparison Between Patients With and Without Coronary Artery Disease

“…Lipoproteins have been shown in in vivo and in vitro models to contribute to a reduction in LPS activity. 15,16) Moreover, it was reported that a low serum TC concentration indicated a worse prognosis in patients with severe heart failure 5,6) in ischemic as well as nonischemic heart diseases. The results of our study and these previous reports had the same conclusions for nonischemic (non-CAD) patients, but the results were quite different in ischemic (CAD) patients.…”