Radioprotection and therapy of radiation injury with cytokines
- Armed Forces Radiobiology Research Institute, Bethesda, MD (USA)
Our results demonstrate that IL 1 promotes hematopoiesis in normal and radiation-compromised animals. IL 1 protected mice from lethal hematopoietic syndrome when given before irradiation. Given therapeutically after irradiation, IL 1 promoted recovery from radiation injury. Several activities of IL 1 may explain its bone marrow restorative properties. The induction with IL 1 of several hematopoietic growth factors (GM-CSF, G-CSF, M-CSF, IL 3, and IL 6) clearly contributes to the accelerated growth and differentiation of hematopoietic progenitor cells. The induction of scavenger proteins may reduce oxidative damage after irradiation. Our work raises a number of additional questions concerning the potential therapeutic utility of IL 1. The ability of IL 1 to promote engraftment of allogeneic bone marrow cells will require further study. The optimal dosage, schedule, and route for IL 1 induction of hematopoiesis will need to be established. The observed synergy of IL 1 with TNF, IL 6, or CSF's may be useful in reducing the requisite doses of cytokines from pharmacological to physiological levels, thus reducing toxic effects. The observation that the cyclooxygenase inhibitor, indomethacin, does not inhibit IL 1 radioprotection may allow us to combat some of the toxic manifestations of IL 1 and to preserve its beneficial actions. Clinical trials with IL 1 in patients, now in progress, should establish whether this cytokine may be useful in reversing the myelotoxic effects of radiotherapy and chemotherapy in humans.
- OSTI ID:
- 6366245
- Journal Information:
- Progress in Clinical and Biological Research; (USA), Vol. 352; ISSN 0361-7742
- Country of Publication:
- United States
- Language:
- English
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BONE MARROW CELLS
TRANSPLANTS
LYMPHOKINES
RADIOSENSITIVITY EFFECTS
GROWTH FACTORS
MICE
RADIATION CHIMERAS
RADIATION INJURIES
RADIATION PROTECTION
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
CHIMERAS
CONNECTIVE TISSUE CELLS
INJURIES
MAMMALS
MITOGENS
MOSAICISM
ORGANIC COMPOUNDS
PROTEINS
RADIATION EFFECTS
RODENTS
SOMATIC CELLS
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560152* - Radiation Effects on Animals- Animals