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Effect of post-treatment with granulocyte colony-stimulating factor on endotoxin-induced lung injury in sheep.

We administered a bolus of G-CSF (250 micrograms/body) just after the infusion of endotoxin (1 microgram/kg) in awake sheep with chronic lung lymph fistula to examine the effect of post-treatment with G-CSF on endotoxin-induced lung injury. We measured pulmonary hemodynamics, lung lymph flow, and concentrations of thromboxane B2 and 6-keto-prostaglandin F1 alpha in plasma and lung lymph. In the G-CSF post-treated group, the pulmonary arterial pressure, pulmonary vascular resistance, and lung lymph flow did not significantly increase in the late period (3-5 h after endotoxin infusion). The arterial oxygen gas tension in the late period was higher in the G-CSF post-treated sheep than in those that received only endotoxin. Although the level of thromboxane B2 in plasma significantly increased at 1 h after endotoxin, the lung lymph flow did not increase much in the G-CSF post-treated group. We conclude that post-treatment with G-CSF instead attenuates the degree of pulmonary vascular leakage on endotoxin-induced lung injury and increased thromboxane B2, the principle metabolite of thromboxane A2, may not exacerbate the injury in awake sheep.