Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Seven-day administration of recombinant human granulocyte colony-stimulating factor to newborn rats: modulation of neonatal neutrophilia, myelopoiesis, and group B Streptococcus sepsis. 169 22

Dysregulation of neonatal myelopoiesis and thrombopoiesis predisposes the newborn to develop neutropenia and/or thrombocytopenia during states of increased demand. We have previously examined the effects of granulocyte colony-stimulating factor (G-CSF) alone or in combination with either stem cell factor (SCF) or interleukin-11 (IL-11) on in vivo neonatal rat hematopoiesis. In this study, we determined the effect of the triple combination of IL-11, SCF, and G-CSF on newborn rat hematopoiesis. Newborn Sprague-Dawley rats (< or = 24 hours old) were administered intraperitoneal (IP) injections of 250 micrograms/kg IL-11, 100 micrograms/kg SCF, 5 micrograms/kg G-CSF, or various combinations or phosphate-buffered saline (PBS)/human serum albumin (HSA) x 14 d. Platelet and blood cell counts were obtained on days 1, 3, 6, 8, 10, and 13; on day 14 bone marrow neutrophil storage pool (BM NSP), neutrophil proliferative pool (NPP), colony-forming units-granulocyte/macrophage (CFU-GM), and CFU-GM proliferative rates were determined. The triple combination failed to significantly increase the circulating hematocrit over other combinations or placebo. The circulating platelet counts, however, significantly increased during each of the IL-11 treatment arms, but they were not enhanced by the addition of either SCF, G-CSF, or the combination. The triple combination of IL-11, SCF, and G-CSF induced the most significant increase in the circulating absolute neutrophil count (ANC) above any other combination or placebo. Circulating ANC increased 12-fold following the triple combination vs. PBS/HSA (day 14 ANC 16525 +/- 1340 vs. 1368 +/- 197) (p < 0.001). The triple combination of IL-11, SCF, and G-CSF also induced the most significant increase in the BM/CFU-GM proliferative rate and BM NPP, p < 0.002 and p < 0.008, respectively. The highest increase in CFU-GM colony formation, however, occurred with both early lineage CSFs, that is, IL-11 plus SCF, and it was not further enhanced by the addition of G-CSF. These data suggest that the combination of two early-lineage CSFs, IL-11 plus SCF and G-CSF, significantly induces newborn rat myelopoiesis and that IL-11 alone significantly induces newborn rat thrombopoiesis. These results may be helpful in the design of future therapies to treat and/or prevent cytopenias in the newborn.
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PMID:The combined effects of interleukin-11, stem cell factor, and granulocyte colony-stimulating factor on newborn rat hematopoiesis: significant enhancement of the absolute neutrophil count. 752 64

Despite advances in the use of newer antimicrobials and aggressive supportive care, sepsis and its sequalae remain a major source of morbidity and mortality in the neonate. The VLBW neonate is especially at high risk. We and others have demonstrated that neonatal MNC are deficient in their production of G-CSF and GM-CSF, which, in part, may explain the neonates propensity to develop neutropenia during times of sepsis. G-CSF and GM-CSF have been shown to both enhance neonatal neutrophil superoxide production in vitro and to increase circulating neutrophil numbers through expansion of the NSP in the BM in neonatal rats and humans. G-CSF is protective (if given with or before antibiotics) during experimental GBS in the neonatal rat and appears to be well tolerated (both short term and 2 years after its use) in the human neonate. In a phase II randomized pilot multicenter study, GM-CSF prophylaxis in the VLBW neonate was well tolerated during 4 weeks of administration and was noted to have significantly reduced the incidence of nosocomial infections. Future efficacy and safety studies in more neonates need to be completed and assessed before the routine pharmacologic use of G-CSF or GM-CSF is recommended to prevent and treat neonatal sepsis.
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PMID:Rationale and potential use of cytokines in the prevention and treatment of neonatal sepsis. 977 42