RG-CSF REDUCES ENDOTOXEMIA AND IMPROVES SURVIVAL DURING ESCHERICHIA-COLI PNEUMONIA

We investigated the effects of recombinant granulocyte colony-stimulat ing factor (rG-CSF) during canine bacterial pneumonia. Beagles with ch ronic tracheostomies received daily subcutaneous rG-CSF (5 mu g/kg bod y wt) or placebo for 14 days, beginning 9 days before intrabronchial i noculation with E. coli. Animals received antibiotics and fluid suppor t; a subset received humidified oxygen (fractional inspired O-2 0.40). Compared with controls, rG-CSF increased circulating neutrophil count s (57.4 vs. 11.0 x 10(3)/mm(3), day 1 after infection; P = 0.0001), de creased plasma endotoxin (7.5 vs. 1.1 EU/ml at 8 h; P < 0.01) and seru m tumor necrosis factor-alpha (3,402 vs. 729 pg/ml at 2 h; P = 0.01) l evels, and prolonged survival (relative risk of death = 0.45, 95% conf idence 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) aft er similar treatment with rG-CSF had lower serum endotoxin levels (7.6 2 vs. 5.81 log EU/ml at 6 h; P < 0.01) and less cardiovascular dysfunc tion (P < 0.05 to < 0.002) but similar tumor necrosis factor-alpha lev els (P = not significant) compared with controls. Thus prophylactic rG -CSF sufficient to increase circulating neutrophils during bacterial p neumonia may improve cardiovascular function and survival by mechanism s that in part enhance the clearance of bacterial toxins but do not im prove lung function.