Synergy of interleukin 1 and granulocyte colony-stimulating factor: in vivo stimulation of stem-cell recovery and hematopoietic regeneration following 5-fluorouracil treatment of mice

Journal Article · Thu Oct 01 00:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.20.7134· OSTI ID:7024994

Moore, M A.S.; Warren, D J

The human bladder carcinoma cell line 5637 produces hematopoietic growth factors (granulocyte and granulocyte/macrophage colony-stimulating factors (G-CSF and GM-CSF)) and hemopoietin 1, which synergizes with CSFs to stimulate colony formation by primitive hematopoietic stem cells in 5-fluorouracil-treated mouse bone marrow. Molecular and functional properties of hemopoietin 1 identified it as identical to interleukin 1..cap alpha.. (IL-1..cap alpha..). When bone marrow cells from 5-fluorouracil-treated mice were cultured in suspension for 7 days with recombinant human IL-1..cap alpha.. and/or G-CSF, it was found that the two factors synergized to enhance recovery of myelopoietic cells and colony-forming cells of both high and low proliferative potential. G-CSF alone did not sustain these populations, but the combination had greater-than-additive stimulating capacity. In vivo, 5-fluorouracil (150 mg/kg) produced profound myelosuppression and delayed neutrophil regeneration for up to 2 weeks in C3H/HeJ mice. Daily administration of recombinant human G-CSF or human IL-1..cap alpha.. accelerated recovery of stem cells, progenitor cells, and blood neutrophils by up to 4 days in 5-fluorouracil-treated C3H/HeJ and B6D2F/sub 1/ mice. The combination of IL-1..cap alpha.. and G-CSF acted synergistically, reducing neutropenia and accelerating recovery of normal neutrophil numbers by up to 7 days. These results indicate the possible therapeutic potential of combination therapy with IL-1 and hematopoietic growth factors such as G-CSF in the treatment of chemotherapy- or radiation-induced myelosuppression.

• Research Organization: Memorial Sloan-Kettering Cancer Center, New York, NY (USA)
• OSTI ID: 7024994
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:20; ISSN PNASA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTIMETABOLITES
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
BONE MARROW CELLS
CARCINOMAS
CELL PROLIFERATION
CHEMOTHERAPY
CONNECTIVE TISSUE CELLS
DISEASES
DRUGS
FLUOROURACILS
GROWTH FACTORS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IMMUNOSUPPRESSION
LEUKOCYTES
LYMPHOKINES
MAMMALS
MAN
MATERIALS
MEDICINE
MICE
MITOGENS
NEOPLASMS
NEUTROPHILS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PRIMATES
PROTEINS
PYRIMIDINES
RADIOLOGY
RADIOTHERAPY
RODENTS
SOMATIC CELLS
STEM CELLS
SYNERGISM
THERAPY
TUMOR CELLS
URACILS
VERTEBRATES