Effects of recombinant human macrophage colony-stimulating factor on plasma cholesterol levels

Abstract

Recombinant human macrophage colony-stimulating factor (rhM-CSF) is a hematopoietic growth factor that stimulates the growth, differentiation, proliferation, and activation of cells of the monocyte/macrophage lineage. rhM-CSF was administered to rabbits and nonhuman primates to evaluate effects on cholesterol homeostasis. Decreases in plasma cholesterol concentrations were observed during rhM-CSF administration. The observed mean (±SD) decreases over a range of doses in nonhuman primates receiving rhM-CSF by continuous intravenous infusion (CIVI) or intravenous bolus (IVB) injection were approximately 16% ± 8% and 43% ± 10%, respectively. Low-density lipoprotein (LDL) cholesterol levels decreased 55% ± 9% from pretreatment baseline values in the animals receiving rhM-CSF by IVB. Normocho-lesterolemic New Zealand white rabbits receiving rhM-CSF over a range of doses by CIVI showed a decrease from baseline in total cholesterol of approximately 28% ± 17%, with LDL cholesterol levels decreasing by approximately 72% ± 33%, while high-density lipoprotein levels showed variable changes, including increased values. A decrease of 36% ± 26% in total plasma cholesterol was observed in Watanabe Heritable Hyperlipidemic rabbits receiving rhM-CSF by CIVI for 7 days. This decrease was attributable almost entirely to decreases in LDL cholesterol, which fell approximately 34% ± 24% from baseline. Although the mechanism of this cholesterol-lowering effect is unknown, these results strongly suggest that rhM-CSF may provide a novel treatment for hypercholesterolemia and may be useful in investigations into the mechanisms of cholesterol homeostasis and atherogenesis. © 1991 by The American Society of Hematology.