Fulton R, Gasper P W, Ogilvie G K, Boone T C, Dornsife R E
Department of Pathology, Colorado State University, College of Veterinary Medicine and Biomedical Sciences, Fort Collins 80523.
Exp Hematol. 1991 Sep;19(8):759-67.
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 micrograms/kg to two cats each s.c. twice daily for 21 days. This resulted in significant (p less than 0.01) elevations of peripheral blood neutrophils from 3.0- to 9.2-fold above pretreatment levels and significantly (p less than 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/microliters to 61,400 cells/microliters (normal is less than 12,500). Lymphocytosis (greater than 7000 lymphocytes/microliters) and monocytosis (greater than 850 monocytes/microliters) 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 less than 0.01) elevated over those of treatment controls on days 12-17. Lymphocyte numbers in rhG-CSF-treated cats were significantly elevated (p less than 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 less than 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 less than 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 microgram rhG-CSF/ml assay.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究的目的是确定重组人粒细胞集落刺激因子（rhG-CSF）如何影响正常猫的造血功能。将重组人G-CSF以3.0、5.0和10.0微克/千克的剂量分别皮下注射给两只猫，每天两次，共21天。这导致外周血中性粒细胞显著（p<0.01）升高，比预处理水平高出3.0至9.2倍，且显著（p<0.02）高于未治疗对照猫（n = 4）的水平。在所评估的任何参数中，在这些剂量下均未观察到统计学上显著的剂量相关反应。中性粒细胞增多的高峰期出现在rhG-CSF治疗的第10天至14天之间，最大中性粒细胞计数范围为20,370个细胞/微升至61,400个细胞/微升（正常范围小于12,500）。在中性粒细胞刺激最大的时期，50%接受rhG-CSF治疗的猫出现淋巴细胞增多（大于7000个淋巴细胞/微升）和单核细胞增多（大于850个单核细胞/微升）。在第12至17天，治疗猫的单核细胞计数显著（p<0.01）高于治疗对照猫。在rhG-CSF治疗的第12天和14天，rhG-CSF治疗猫的淋巴细胞数量显著高于预处理对照猫（p<0.05）。网织红细胞计数、血小板计数或血细胞比容水平未观察到显著变化。到第19天，中性粒细胞水平已从最大中性粒细胞水平显著下降（p<0.01），在rhG-CSF治疗的第21天，有一只猫的血液中性粒细胞计数恢复正常。骨髓穿刺显示，在rhG-CSF治疗的猫中，直至治疗第14天骨髓细胞总数总体增加，骨髓髓系与红系比例比未治疗对照猫增加了2至9倍。从第0天到第14天，骨髓中的红系和淋巴系成分减少，而早期髓系祖细胞（原粒细胞、早幼粒细胞和中幼粒细胞）显著增加（p<0.05）。在整个治疗期间，骨髓中晚期髓系细胞的百分比未观察到显著差异。对治疗猫获得的骨髓进行体外集落形成试验显示，直至第14天粒细胞-巨噬细胞集落形成单位（CFU-GM）增加，随后在rhG-CSF治疗的第21天减少。在一项稀释研究中，重组人G-CSF对未治疗猫的猫骨髓细胞也有体外刺激作用，在0.1微克rhG-CSF/毫升的测定中CFU-GM形成最大。（摘要截取自400字）
