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Administration of erythropoietin to newborn rats results in diminished
neutrophil production
RD Christensen, KW Liechty, JM Koenig, KR Schibler and RK Ohls
Division of Human Development and Aging, University of Utah School of
Medicine, Salt Lake City 84132.
Very high concentrations of erythropoietin (epo), in clonogenic cultures,
result in reduced production of neutrophils, and fetal progenitors are more
sensitive to this effect of epo than are those of adults. However, the
significance of this observation is unclear because no evidence of reduced
neutrophil production has been presented following administration of
recombinant epo to human or animal subjects. In the present study we
injected newborn rats, beginning on the first day of life, with 20, 200, or
2,000 U epo/kg body weight, and measured serum epo concentrations after 2,
8, 24, or 48 hours. After selecting a dose that resulted in serum
concentrations greater than 1,000 mU/mL (a concentration that resulted in
down-modulation of neutrophil production from neonatal rat progenitors in
vitro) other newborn rats were treated for 3 days with that dose (1,000 U
epo/kg) or a vehicle control. Administration of epo resulted in increased
hematocrits (P less than .001), reticulocyte counts (P less than .001),
normoblasts/femur (P less than .05), and normoblasts/spleen (P less than
.001). Recipients of epo also had more erythroid colony-forming units
(CFU-E) (P less than .001) and higher CFU-E tritiated thymidine suicide
rates (P less than .01) than did controls. However, femurs and spleens of
epo recipients contained fewer postmitotic neutrophils (femur, P less than
.01; spleen, P less than .01), proliferative neutrophils (femur, P less
than .01; spleen, P less than .02), granulocyte-macrophage colony-forming
units (CFU-GM) (P less than .005), and lower CFU-GM tritiated thymidine
suicide rates (P less than .01). Seven and nine days after twice-daily
administration of 2,000 U epo/kg, blood neutrophil concentrations had
diminished (P less than .05). Thus, administration of high doses of
recombinant epo to newborn rats resulted in diminished neutrophil
production accompanying accelerated erythropoiesis.
Volume 78,
Issue 5,
pp. 1241-1246,
09/01/1991
Copyright © 1991 by The American Society of Hematology
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