GRANULOCYTE-COLONY-STIMULATING FACTOR DOES NOT EXACERBATE ENDOTOXIN-INDUCED LUNG INJURY IN SHEEP

Because it has been suggested that neutrophils play a role in endotoxin-induced lung injury, we examined the effects of increased peripheral blood-neutrophils induced by recombinant human granulocyte-colony-stimulating factor (rhG-CSF) on the lung dysfunction when induced by endotoxin in awake sheep. We prepared chronically instrumented awake sheep with lung lymph fistulae and catheters for hemodynamic monitoring. We compared alterations of pulmonary hemodynamics, lung lymph balance, circulating leukocytes, plasma and lung lymph concentrations of thromboxane B2 and 6-keto-prostaglandin F1alpha, and arterial blood gases in sheep that received Escherichia coli endotoxin infusion intravenously (1 mug/kg) in the following two groups: Group 1 (n = 6) received endotoxin alone, and Group 2 (n = 7) received rhG-CSF (125 mug/day) intravenously for 3 days before endotoxin was administered in the same manner as in Group 1. The rhG-CSF remarkably increased circulating neutrophils to 24,600 +/- 2,500/mul in Group 2 sheep at baseline when compared with the level in Group 1 (5,700 +/- 550 mul). After endotoxin infusion, we observed significant decreases in circulating neutrophils in both groups. There were no differences between the two groups in the time course of changes in pulmonary hemodynamics, arterial blood gases, or arachidonate products after endotoxemia. However, lung lymph flow and lung lymph protein clearance during the late phase were lower in rhG-CSF-treated sheep than in those that received only endotoxin. These data suggested that increased circulating neutrophils induced by rhG-CSF did not enhance endotoxin-induced lung injury in awake sheep and that they may be associated with a reduction in the late lung lymph flow changes.