Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
THE COLONY STIMULATING FACTORS: MOLECULAR, CELLULAR AND CLINICAL ASPECTS
Int Congress Ser; (925):333-47 1990. Unique Identifier : AIDSLINE ICDB/92679909 Metcalf D; The Walter and Eliza Hall Inst. of Medical Res., P.O. Royal; Melbourne Hosp., 3050 Victoria, Australia
Abstract:
Each cell division by granulocyte-macrophage precursors has been shown to require active stimulation. Four distinct molecules are associated with this biological activity; the four known colony-stimulating factors (CSFs) are granulocyte (G)-CSF, a relatively selective stimulus for granulocyte formation, macrophage (M)-CSF for monocyte-macrophage formation, and GM-CSF and multi-CSF (IL-3), which can stimulate the formation of both granulocytes and macrophages. CSFs are reviewed, including CSFs and their receptors, in vitro actions of the CSFs, the biology of the CSFs, in vivo effect of the CSFs, clinical trials of the CSFs, and disease states based on CSF abnormalities. The CSFs are highly active agents and stimulate cell proliferation in the 10(-10) to 10(-12) M range. As CSF concentrations increase, a broader range of lineages tends to be stimulated. The production of CSFs in active recombinant form has allowed a variety of animal and clinical studies demonstrating their effectiveness in increasing the production of these cells and enhancing resistance to infections. Multiple clinical trials have established that the injection of CSF is most effective by the sc route and results in a dose-related rise in blood granulocytes in the case of G-CSF or in granulocytes, monocytes, and eosinophils in the case of GM-CSF. Similar, but somewhat reduced, responses can be elicited in patients (pts) with hypoplastic bone marrow from prior treatment with myelotoxic drugs. In pts who have received marrow transplants, injection of CSFs accelerates hemopoietic regeneration by 7-10 days, reducing the period of dangerous neutropenia. An early study documented the ability of GM-CSF to elevate neutrophil and monocyte levels in AIDS pts, but no data have been produced yet on whether enhanced resistance to secondary infections was achieved. The role of the CSFs in myeloid leukemia is more complex than in infectious disease because CSFs are necessary for the emergence of the leukemic clone yet have the ability to suppress leukemic cells by enforced maturation. No trials have been initiated on such pts using CSF therapy alone, but early studies using a combination of chemotherapy with CSF treatment appeared to show an additional benefit of CSF in forcing a higher population of leukemic cells to enter the cell cycle and become susceptible to cell cycle-specific cytotoxic agents. (48 Refs)
Keywords: Acquired Immunodeficiency Syndrome/METABOLISM Bone Marrow/PATHOLOGY Bone Marrow Transplantation Cell Cycle Colony-Stimulating Factors/*METABOLISM/PHARMACOLOGY Eosinophils/*METABOLISM Granulocyte Colony-Stimulating Factor/*METABOLISM/PHARMACOLOGY Granulocyte-Macrophage Colony-Stimulating Factor/*METABOLISM/ PHARMACOLOGY Granulocytes/*METABOLISM Hematopoietic Stem Cells/CYTOLOGY Human Leukemia, Myeloid/PATHOLOGY Macrophage Colony-Stimulating Factor/*METABOLISM/PHARMACOLOGY Monocytes/*METABOLISM CLINICAL TRIAL MEETING PAPER
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
