In vivo hematologic effects of recombinant human macrophage colony-stimulating factor.
Macrophage colony-stimulating factor (recombinant human M-CSF) given as a single intravenous injection to Lewis rats induces a dose-dependent peripheral monocytosis, neutrophilia, and lymphopenia. The monocytosis peaks at 28 to 32 hours with a seven- to eightfold increase in the number of circulating monocytes and promonocytes. The peripheral monocytosis is accompanied by a slight increase in marrow blasts, promonocytes, and monocytes. A monocytopenia reaching a nadir at 15 minutes precedes the monocytosis, suggesting that M-CSF activates circulating monocytes and causes intravascular margination. The M-CSF-induced neutrophilia and lymphopenia are relatively mild in magnitude, are observed between 2 and 16 hours after injection, and are no longer evident at later time-points. The monocytosis was at least partially inhibited by dexamethasone. M-CSF-induced monocytosis most likely reflects a direct effect of M-CSF on marrow monocyte precursor proliferation, maturation, and release, whereas the neutrophilia and lymphopenia may reflect indirect effects mediated by the known ability of M-CSF to cause the release of other cytokines.
Department of Pathology, University of California, Irvine 92717.
T R
TR
Ulich
J
J
del Castillo
L R
LR
Watson
S M
SM
Yin
M B
MB
Garnick
D000818:Animals; D002452:Cell Count / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D007962:Leukocytes / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor