Frenck R W, Sarman G, Harper T E, Buescher E S
Department of Pediatrics, University of Texas Medical School, Houston 77030.
J Infect Dis. 1990 Jul;162(1):109-14. doi: 10.1093/infdis/162.1.109.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) potentiates in vitro and in vivo production of granulocytes. Also, recombinant human GM-CSF in vitro enhances functional capabilities of human granulocytes. Recombinant murine (rm) GM-CSF was administered to neonatal rats in vivo to test its ability to protect from septic death due to Staphylococcus aureus. When rmGM-CSF was given intraperitoneally 6 h before a 90% lethal dose challenge of S. aureus, peak survival was observed at a dose of 30 pg/g (54% vs. 10% in animals administered saline; P less than .001). Blood cultures were positive for S. aureus in 26 of 32 saline-treated and in 5 of 31 rmGM-CSF-treated animals (P less than .001). Numbers of blood granulocytes were significantly increased 9 h after administration of rmGM-CSF (30 pg/g) but returned to control levels by 12 h. Neither neutrophil storage nor proliferative pools were affected. Thus, rmGM-CSF significantly improved survival when given prophylactically in a neonatal rat model of infection.
粒细胞-巨噬细胞集落刺激因子(GM-CSF)可增强体外和体内粒细胞的生成。此外,重组人GM-CSF在体外可增强人粒细胞的功能。将重组鼠(rm)GM-CSF给新生大鼠进行体内给药,以测试其预防金黄色葡萄球菌所致败血症死亡的能力。当在给予90%致死剂量的金黄色葡萄球菌攻击前6小时腹腔内注射rmGM-CSF时,在剂量为30 pg/g时观察到最高存活率(生理盐水处理的动物为10%,而rmGM-CSF处理的动物为54%;P小于0.001)。32只生理盐水处理的动物中有26只血培养金黄色葡萄球菌呈阳性,31只rmGM-CSF处理的动物中有5只血培养金黄色葡萄球菌呈阳性(P小于0.001)。给予rmGM-CSF(30 pg/g)后9小时,血粒细胞数量显著增加,但到12小时时恢复到对照水平。中性粒细胞储存池和增殖池均未受影响。因此,在新生大鼠感染模型中预防性给予rmGM-CSF可显著提高存活率。