Eichacker P Q, Waisman Y, Natanson C, Farese A, Hoffman W D, Banks S M, MacVittie T J
Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, Bethesda 20814.
J Appl Physiol (1985). 1994 Nov;77(5):2366-73. doi: 10.1152/jappl.1994.77.5.2366.
We investigated the effects of recombinant granulocyte colony-stimulating factor (G-CSF) in a canine model of septic shock. Awake 2-yr-old beagles were studied before and after intraperitoneal placement of an Escherichia coli-infected clot. Nine days before and until 3 days after clot placement, animals received daily high-dose (G-CSF (5 microgram/kg body wt; n = 17), low-dose G-CSF (0.1 microgram/kg body wt; n = 17), or a control protein (5 micrograms/kg body wt; n = 20). Survival rate was greater (P < 0.04, Wilcoxon test) in the high-dose G-CSF group (14/17) than in the low-dose G-CSF (10/17) and control (12/20) groups. High-dose G-CSF improved cardiovascular function, as evidenced by increased left ventricular ejection fraction (day 1 after clot; P < 0.001) and mean arterial pressure (day 2; P < 0.02) compared with low-dose G-CSF and control groups. High-dose G-CSF increased (P < 0.001) mean peripheral neutrophils before (-3 days) and after (2 h to 4 days) clot and produced a more rapid (P < 0.001) rise (day 2) and fall (day 4) in mean alveolar neutrophil numbers compared with the low-dose G-CSF and control groups. High-dose G-CSF decreased mean serum endotoxin (2-8 h; P < 0.002) and tumor necrosis factor (2 h; P < 0.02) levels and lowered blood bacteria counts (2-6 h; P < 0.04) compared with the low-dose G-CSF and control groups. Thus, in this canine model, G-CSF sufficient to increase peripheral neutrophils before and during peritonitis and septic shock enhances host defense, reduces cytokine (tumor necrosis factor) levels, and improves cardiovascular function and survival.
我们在犬类脓毒性休克模型中研究了重组粒细胞集落刺激因子（G-CSF）的作用。对清醒的2岁比格犬在腹腔内放置感染大肠杆菌的血凝块前后进行了研究。在放置血凝块前9天直至放置后3天，动物每天接受高剂量G-CSF（5微克/千克体重；n = 17）、低剂量G-CSF（0.1微克/千克体重；n = 17）或对照蛋白（5微克/千克体重；n = 20）。高剂量G-CSF组（14/17）的存活率高于低剂量G-CSF组（10/17）和对照组（12/20）（P < 0.04，Wilcoxon检验）。与低剂量G-CSF组和对照组相比，高剂量G-CSF改善了心血管功能，表现为左心室射血分数增加（血凝块放置后第1天；P < 0.001）和平均动脉压升高（第2天；P < 0.02）。高剂量G-CSF在血凝块放置前（-3天）和放置后（2小时至4天）增加了外周平均中性粒细胞数量（P < 0.001），与低剂量G-CSF组和对照组相比，平均肺泡中性粒细胞数量上升（第2天）和下降（第4天）更快（P < 0.001）。与低剂量G-CSF组和对照组相比，高剂量G-CSF降低了平均血清内毒素水平（2 - 8小时；P < 0.002）和肿瘤坏死因子水平（2小时；P < 0.02），并降低了血细菌计数（2 - 6小时；P < 0.04）。因此，在这个犬类模型中，足以在腹膜炎和脓毒性休克之前及期间增加外周中性粒细胞的G-CSF可增强宿主防御、降低细胞因子（肿瘤坏死因子）水平，并改善心血管功能和存活率。
