Neutrophils Pretreated with Granulocyte Colony-Stimulating Factor (G-CSF) are not Related to the Severity of Endotoxin-Induced Lung Injury

Abstract

Neutrophils play an important role in mediating acute lung injury that is characteristic of adult respiratory distress syndrome. Granulocyte colony-stimulating factor (G-CSF) has been shown to increase neutrophil counts and to enhance their biological functions. This study investigated the effects of neutrophils pretreated with G-CSF on endotoxin-induced lung injury in conscious sheep. Nineteen sheep were chronically instrumented with a lung lymph fistula and vascular catheters for monitoring. Sheep were randomly allocated into three groups: group 1-sheep were infused only with endotoxin; group 2-G-CSF (250 μg/day) was administered intravenously for 5 days prior to endotoxin; and group 3-GCSF (125 μg) was administered just before endotoxin. In each group, sheep received E. coli endotoxin (1 μg/kg) for 30 min and observations were made for 5 h after endotoxin administration. Circulating leukocyte counts before endotoxin markedly increased in group 2 and significantly decreased in group 3, when compared with the level in group 1 (9700 ± 900 (SEM) in group 1, 49,900 ± 10,000 in group 2, and 3600 ± 600/μL in group 3). In each group, circulating leukocyte counts significantly decreased 1 h after endotoxin administration and then returned to baseline values. However, there were no significant differences in either pulmonary hemodynamic or lung lymph responses to endotoxin among the groups. The results indicate that G-CSF does not adversely affect physiologic responses of the lung to endotoxin in sheep.