EFFECT OF RECOMBINANT HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR ON HEMATOPOIESIS IN NORMAL CATS

The objective of this study was to determine how recombinant human granulocyte colony-stimulating factor (rhG-CSF) affects hematopoiesis in normal cats. Recombinant human G-CSF was given at 3.0, 5.0, and 10.0-mu-g/kg to two cats each s.c. twice daily for 21 days. This resulted in significant (p < 0.01) elevations of peripheral blood neutrophils from 3.0- to 9.2-fold above pretreatment levels and significantly (p < 0.02) above levels of nontreated control cats (n = 4). A statistically significant dose-related response was not seen at these dosages in any parameter evaluated. The period of maximum neutrophilia occurred between days 10 and 14 of rhG-CSF treatment, with maximum neutrophil counts ranging from 20,370 cells/mu-l to 61,400 cells/mu-l (normal is < 12,500). Lymphocytosis (> 7000 lymphocytes/mu-l) and monocytosis (> 850 monocytes/mu-l) were observed in 50% of the cats receiving rhG-CSF during the period of maximal neutrophil stimulation. Monocyte counts in treated cats were significantly (p < 0.0 1) elevated over those of treatment controls on days 12-17. Lymphocyte numbers in rhG-CSF-treated cats were significantly elevated (p < 0.05) over pretreatment controls on days 12 and 14 of rhG-CSF treatment. No significant changes were observed in reticulocyte counts, platelet counts, or hematocrit levels. By day 19, neutrophil levels had dropped significantly (p < 0.01) from the maximum neutrophil levels, with one cat attaining a normal blood neutrophil count by day 21 of rhG-CSF treatment. Marrow aspirates revealed an overall increase in marrow cellularity through day 14 of treatment in rhG-CSF-treated cats, with increased myeloid : erythroid ratios (two- to ninefold) over those of nontreated controls. The erythroid and lymphoid component of the marrow decreased from day 0 to day 14, whereas the early myeloid progenitors (myeloblasts, progranulocytes, and myelocytes) increased significantly (p < 0.05). No significant differences in the percentage of later myeloid forms in the marrow were observed over the treatment period. In vitro colony-forming assays of marrow obtained from treated cats revealed increases in granulocyte-macrophage colony-forming units (CFU-GM) through day 14, with subsequent decreases by day 21 of rhG-CSF treatment. Recombinant human G-CSF was also effective at in vitro stimulation of feline marrow cells from untreated cats in a dilution study, with maximal CFU-GM formation at 0.1-mu-g rhG-CSF/ml assay. These results indicate that rhG-CSF causes relatively short-term (< 3 weeks) significant increases in peripheral blood neutrophils, lymphocytes, and monocytes at 3-, 5-, and 10-mu-g/kg doses. There may be a use for rhG-CSF in the short-term treatment of neutropenias in cats with diseases such as feline parvovirus infection or in cats receiving marrow-ablative therapies such as cancer chemotherapy or marrow transplant therapy.