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)

Studies were carried out to establish the temporal effects of abbreviated administrations of IL-1 and IL-1 plus M-CSF as rescue agents on multipotential and short-term repopulating hematopoietic stem cell (HSC) subpopulations in murine marrow treated with a myelosuppressive dose of 150 mg/kg 5-FU. The recovery kinetics for high-proliferative-potential colony-forming cells (HPP-CFC), CFU-S8 and -S12, and both CFU-M and CFU-G compartments were monitored over a 14-day interval in 5-FU-treated bone marrow (FUBM) following daily cytokine injections over a 4-day interval. Both IL-1 and the coadministration of IL-1 and M-CSF rapidly enhanced the recovery of the HPP-CFC in FUBM to supranormal levels and maintained these levels for extended intervals. Moreover, since M-CSF was unable to influence the recovery of the HSC subpopulations in FUBM by itself, the results of the two cytokines amounted to a synergistic effect on the recovery of the HPP-CFC in FUBM and a reduction of severe neutropenia in the myelosuppressed animal. Scheduling studies demonstrated that these synergistic effects were restricted to those schedules in which M-CSF was coadministered with IL-1 during the first 2 days of cytokine rescue. Finally, the recovery curves generated for the HSC and CFU-M subpopulations in response to IL-1 (with or without M-CSF) also suggest that these cytokines may conceivably alter the normal balance between proliferation and differentiation within CFU-S8 and -S12 during the accelerated recovery of hematopoiesis in FUBM.
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PMID:Temporal recovery of short-term repopulating HSC subpopulations in marrow following schedule-dependent administrations of IL-1 alpha and M-CSF. 763 81

G-CSF is routinely used to hasten recovery from chemotherapy-induced neutropenia. We have recently shown that G-CSF, when combined with stem cell-damaging cytotoxic agents, results in enhanced stem cell damage and loss of marrow reserve. To investigate the mechanisms of stem cell damage caused by G-CSF, we gave C57BL/6 (B6) mice repeated doses of cyclophosphamide ([CY] 84 mg/kg) or carmustine ([BCNU] 13.2 mg/kg) and G-CSF (250 microg/kg/day) for either four days or eight days. Two different regimens of G-CSF were chosen to study the influence of increased proliferation on hematopoiesis which was measured at the end of the first, third and sixth 14-day cycle of each cytotoxic agent and 7 and 20 weeks after completion of all cycles. A spectrum of hematopoietic indices was measured including WBC, bone marrow cellularity, granulocyte/macrophage-colony-forming cells (GM-CFC), colony-forming cells with high proliferative-potential (HPP-CFC), cobblestone area-forming cells ([CAFC]-day 7 and CAFC-day 28), and long-term marrow repopulating ability in vivo. Despite the absence of differences in peripheral blood cell counts or bone marrow cellularity 14 days after each dose, progenitor cell levels (HPP-CFC, GM-CFC, and CAFC-7) were increased up to 2.5-fold with cytotoxic agent and G-CSF administration compared with cytotoxic agent administration alone. Mice given G-CSF for eight days had the greatest number of progenitors suggesting a dose-response relationship for G-CSF administration. G-CSF resulted in a decrease in hematopoietic stem cell (CAFC-28) content when measured two weeks after each cycle of saline, CY, and BCNU. Twenty weeks after six cycles of BCNU, the reduction in stem cell levels persisted and was further decreased when G-CSF was added to BCNU for four or eight days. Data from this study suggest that the most likely explanation for the damaging effects of G-CSF is that G-CSF directly or indirectly induces stem cells to differentiate into more committed hematopoietic cells resulting in a loss of marrow reserve. This effect is enhanced in animals with an already compromised hematopoietic stem cell compartment as seen with repeated doses of BCNU.
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PMID:Granulocyte-colony stimulating factor impedes recovery from damage caused by cytotoxic agents through increased differentiation at the expense of self-renewal. 1074 84