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Seven-day administration of recombinant human granulocyte colony-
stimulating factor to newborn rats: modulation of neonatal neutrophilia,
myelopoiesis, and group B Streptococcus sepsis
MS Cairo, JM Plunkett, D Mauss and C Van de ven
Division of Hematology-Oncology, Childrens Hospital of Orange County,
University of California, Irvine 92668.
Single-pulse administration of rhG-colony-stimulating factor (CSF) to
neonatal rats was previously demonstrated to induce peripheral neutrophilia
and modulate bone marrow (BM) neutrophil storage and proliferative pools
(NSP + NPP). In this study, we investigated the prolonged effects of 7 days
of rhG-CSF therapy (5 micrograms/kg/per day). Sprague-Dawley newborn rats
(less than or equal to 24 hours) were injected intraperitoneally (IP)
(daily for 7 days) with rhG-CSF or phosphate-buffered saline/human serum
albumin (PBS/HSA). RhG-CSF induced a significant early and late peripheral
neutrophilia: 6,905 +/- 1,625 (day 1) and 9,223 +/- 515 microL (day 7) v
1,275 +/- 90/microL (P less than or equal to .0001). In addition, 7 days of
rhG-CSF resulted in a significant increase in the BM NSP: 3,247 +/-
190/microL v 1,677 +/- 339/microL (P less than or equal to .001). There
was, however, no depletion or significant change in the BM NPP. Seven days
of rhG-CSF also induced a mild increase in BM CFU-GM colony formation (P
less than or equal to .01). There was, however, no significant change in
liver/spleen CFU-GM colonies or in the CFU-GM proliferative rate in either
the BM or liver/spleen cultures. Finally, 7 days of prophylactic rhG-CSF
therapy resulted in a synergistic response with antibiotic therapy and
significantly modulated the mortality rate during experimental group B
streptococcal sepsis (GBS) (100% v 50%) (GvsC) (P less than or equal to
.001). Pulse rhG-CSF administered at 6 hours or 18 hours after GBS
inoculation, however, failed to act synergistically with antibiotics to
improve survival or prevent peripheral neutropenia. This study suggests
that 7 days of prophylactic rhG-CSF therapy induces peripheral
neutrophilia, myeloid maturation, increases neutrophil BM reserves and also
may provide immunologic enhancement of neonatal host defense during
experimental GBS in term neonatal rats.
Volume 76,
Issue 9,
pp. 1788-1794,
11/01/1990
Copyright © 1990 by The American Society of Hematology
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