Effect of Recombinant Human Granulocyte Colony-Stimulating Factor on Hematopoiesis of Normal Dogs and on Hematopoietic Recovery After Otherwise Lethal Total Body Irradiation

• Published in: Blood 1989-09, Vol.74 (4), p.1308-1313
• Main Authors: Schuening, Friedrich G., Storb, Rainer, Goehle, Sondra, Graham, Theodore C., Appelbaum, Frederick R., Hackman, Robert, Souza, Lawrence M.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bone Marrow - drug effects; Bone Marrow - radiation effects; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Colony-Stimulating Factors - pharmacology; Dogs; Dose-Response Relationship, Radiation - drug effects; Female; Fundamental and applied biological sciences. Psychology; Granulocyte Colony-Stimulating Factor; Hematopoiesis - drug effects; Hematopoiesis - radiation effects; Humans; Male; Molecular and cellular biology; Radiation Chimera; Recombinant Proteins - pharmacology; Whole-Body Irradiation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V74.4.1308.1308

This study was designed to test whether recombinant human G-CSF (rh G-CSF) affects hematopoiesis in normal dogs and, if so, to test the effects of G-CSF in dogs given otherwise lethal total body irradiation (TBI). Rh G-CSF given subcutaneously at 10 or 100 μg/kg/d for 14 days to two normal dogs increased peripheral blood neutrophils eight to tenfold and monocytes four to sixfold above controls. Lymphocyte counts remained unchanged at the lower dose and increased threefold at the higher dose of rh G-CSF. No significant changes were observed in eosinophil, platelet, reticulocyte, or hematocrit levels. After 2 weeks of treatment with rh G-CSF, bone marrow displayed myeloid hyperplasia and left-shifted granulocytopoiesis. After discontinuation of rh G-CSF, peripheral leukocyte counts returned to control levels within three days. Five dogs administered 400 cGy TBI at 10 cGy/min from two opposing 60Co sources and no marrow infusion or growth factor, all developed profound pancytopenia and died between 17 and 23 days after TBI with infections secondary to marrow aplasia. Four of five dogs treated within two hours after 400 cGy TBI with 100 μg rh G-CSF/kg/d subcutaneously twice a day for 21 days showed complete and sustained endogenous hematopoietic recovery. In contrast, five dogs irradiated with 400 cGy TBI and treated with 100 μg rh G-CSF/kg/d starting on day 7 after TBI, all died between days 17 and 20 after TBI with infections secondary to marrow aplasia. Rh G-CSF, if administered shortly after irradiation, can reverse the otherwise lethal myelosuppressive effect of radiation exposure.