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Effects of recombinant human macrophage colony-stimulating factor on plasma
cholesterol levels
JB Stoudemire and MB Garnick
Genetics Institute, Cambridge, MA 02140-2387.
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. Normocholesterolemic 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.
Volume 77,
Issue 4,
pp. 750-755,
02/15/1991
Copyright © 1991 by The American Society of Hematology
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