rG-CSF reduces endotoxemia and improves survival duringE. colipneumonia

Abstract

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 O20.40). 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-α (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-α 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.