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Vol. 83, Issue 5, 1467-1475, 1997
Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892-1662
Received 19 August 1996; accepted in final form 23 May 1997.
Freeman, Bradley D., Zenaide Quezado, Fabrice Zeni, Charles
Natanson, Robert L. Danner, Steven Banks, Marcello Quezado, Yvonne
Fitz, John Bacher, and Peter Q. Eichacker. rG-CSF reduces endotoxemia and improves survival during E. coli pneumonia. J. Appl.
Physiol. 83(5): 1467-1475, 1997.
We investigated
the effects of recombinant granulocyte colony-stimulating factor
(rG-CSF) during canine bacterial pneumonia. Beagles with chronic
tracheostomies received daily subcutaneous rG-CSF (5 µg/kg body wt)
or placebo for 14 days, beginning 9 days before intrabronchial
inoculation with E. coli. Animals
received antibiotics and fluid support; a subset received humidified
oxygen (fractional inspired O2
0.40). Compared with controls, rG-CSF increased circulating neutrophil counts (57.4 vs. 11.0 × 103/mm3,
day 1 after infection;
P = 0.0001), decreased plasma
endotoxin (7.5 vs. 1.1 EU/ml at 8 h; P < 0.01) and serum tumor necrosis factor-
(3,402 vs.
729 pg/ml at 2 h; P = 0.01) levels,
and prolonged survival (relative risk of death = 0.45, 95% confidence
interval 0.21-0.97; P = 0.038).
Also, rG-CSF attenuated sepsis-associated myocardial dysfunction
(P < 0.001). rG-CSF had no effect on
pulmonary function or on blood and lung bacteria counts (all
P = not significant). Other animals
challenged with endotoxin (4 mg/kg iv) after similar treatment with
rG-CSF had lower serum endotoxin levels (7.62 vs. 5.81 log EU/ml at 6 h; P < 0.01) and less cardiovascular
dysfunction (P < 0.05 to < 0.002)
but similar tumor necrosis factor- levels (P = not significant) compared with
controls. Thus prophylactic rG-CSF sufficient to increase circulating
neutrophils during bacterial pneumonia may improve cardiovascular
function and survival by mechanisms that in part enhance the clearance
of bacterial toxins but do not improve lung function.
neutrophil; endotoxin; recombinant granulocyte colony-stimulating factor; sepsis; septic shock; Escherichia coli
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