Cardiopulmonary effects of granulocyte colony-stimulating factor in a canine model of bacterial sepsis

• Published in: Journal of applied physiology (1985) Vol. 77; no. 5; p. 2366
• Main Authors: Eichacker, P Q, Waisman, Y, Natanson, C, Farese, A, Hoffman, W D, Banks, S M, MacVittie, T J
• Format: Journal Article
• Language: English
• Published: United States 01.11.1994
• Subjects: Animals; Blood Gas Analysis; Bronchoalveolar Lavage Fluid - immunology; Colony Count, Microbial; Dogs; Endotoxins - blood; Escherichia coli - isolation & purification; Escherichia coli Infections - immunology; Escherichia coli Infections - microbiology; Escherichia coli Infections - physiopathology; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - pharmacology; Hemodynamics; Leukocyte Count; Neutrophils - immunology; Recombinant Proteins - pharmacology; Shock, Septic - immunology; Shock, Septic - microbiology; Shock, Septic - physiopathology; Stroke Volume; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 8750-7587
• 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.