Cardiopulmonary effects of granulocyte colony-stimulating factor in a canine model of bacterial sepsis.
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.
Eichacker
P Q
PQ
Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, Bethesda 20814.
Waisman
Y
Y
Natanson
C
C
Farese
A
A
Hoffman
W D
WD
Banks
S M
SM
MacVittie
T J
TJ
D000818:Animals; D001784:Blood Gas Analysis; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D015169:Colony Count, Microbial; D004285:Dogs; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics; D007958:Leukocyte Count; D009504:Neutrophils / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012772:Shock, Septic / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D013318:Stroke Volume; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor