A comparison of treatment of canine cyclic hematopoiesis with recombinant
human granulocyte-macrophage colony-stimulating factor (GM- CSF), G-CSF
interleukin-3, and canine G-CSF
WP Hammond, TC Boone, RE Donahue, LM Souza and DC Dale
Department of Medicine, University of Washington School of Medicine Seattle
98195.
Cyclic hematopoiesis in gray collie dogs is a stem cell disease in which
abnormal regulation of cell production in the bone marrow causes cyclic
fluctuations of blood cell counts. In vitro studies demonstrated that
recombinant human granulocyte-macrophage colony-stimulating factor
(GM-CSF), interleukin-3 (IL-3), and granulocyte colony stimulating factor
(G-CSF) all stimulated increases in colony formation by canine bone marrow
progenitor cells. Based on these results, gray collie dogs were then
treated with recombinant human (rh) GM-CSF, IL-3, or G-CSF subcutaneously
to test the hypothesis that pharmacologic doses of one of these
hematopoietic growth factors could alter cyclic production of cells. When
recombinant canine G-CSF became available, it was tested over a range of
doses. In vivo rhIL-3 had no effect on the recurrent neutropenia but was
associated with eosinophilia, rhGM-CSF caused neutrophilia and eosinophilia
but cycling of hematopoiesis persisted. However, rhG-CSF caused
neutrophilia, prevented the recurrent neutropenia and, in the two animals
not developing antibodies to rhG- CSF, obliterated periodic fluctuation of
monocyte, eosinophil, reticulocyte, and platelet counts. Recombinant canine
G-CSF increased the nadir neutrophil counts and amplitude of fluctuations
at low doses (1 micrograms/kg/d) and eliminated all cycling of cell counts
at high doses (5 and 10 micrograms/kg/d). These data suggest significant
differences in the actions of these growth factors and imply a critical
role for G-CSF in the homeostatic regulation of hematopoiesis.
Volume 76,
Issue 3,
pp. 523-532,
08/01/1990
Copyright © 1990 by The American Society of Hematology
