Human Granulocyte‐Macrophage Colony‐Stimulating Factor Lowers the Levels of Plasma Cholesterol with an Increase in mRNA for Very Low Density Lipoprotein Receptor in Rabbits a

Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes the proliferation of progenitor cells in the granulocyte-macrophage lineage and stimulates the function of the mature cells. It has been shown that the levels of cholesterol are reduced by the administration of macrophage colony-stimulating factor (M-CSF) or GM-CSF to animals and humans.'-' The mechanisms by which M-CSF lowers plasma cholesterol levels have been extensively However, little is known about the effects of GM-CSF on cholesterol homeostasis and its mechanism(s). We tested the ability of human GM-CSF on lipid metabolism in rabbits and attempted to determine the mechanism(s) of the cholesterol-lowering effect. Twenty pg/kg per day of human GM-CSF was administered subcutaneously to normal and cholesterol-fed rabbits daily in two divided doses for 12 days. An equal dose of human serum albumin (HSA) served as control. The administration of human GM-CSF markedly lowered the levels of plasma cholesterol and triglycerides (n = 6), whereas HSA produced no significant changes in plasma lipid content (n = 9). The levels of total cholesterol were decreased by 51 2 19% (mean ? SD) of pretreatment values ( p < 0.01) with a 47 * 27% decrease in triglycerides ( p < 0.01) in the normal rabbits. The reduction in plasma cholesterol was primarily attributed to a marked lowering of both low-density lipoprotein (LDL) and very-low-density