Granulocyte Colony-Stimulating Factor Enhances Pulmonary Host Defenses in Normal and Ethanol-Treated Rats

Authors:
  • WSWarren Summer
    Warren Summer
  • GBGregory Bagby
    Gregory Bagby
  • CNChester Nakamura
    Chester Nakamura
  • LSLaura Stewart
    Laura Stewart
  • GLGary Lipscomb
    Gary Lipscomb
  • JAJeff Andresen
    Jeff Andresen
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Abstract
Ethanol suppresses functions of the polymorphonuclear leukocyte (PMNL), seriously compromising normal host defenses against pneumonia. Because granulocyte colony-stimulating factor (G-CSF) augments the number and function ofPMNL, the effect ofG-CSF on the antibacterial defenses of the lung in normal and acutely intoxicated rats was studied. Animals received G-CSF or vehicle twice a day for 2 days, then ethanol or saline, followed by challenge with Klebsiella pneumoniae. K. pneumoniae elicited an intrapulmonary influx of PMNL in control rats that was markedly suppressed by prior ethanol administration. G-CSF augmented the recruitment of PMNL into the lungs of control rats and significantly attenuated the adverse effects of ethanol on PMNL entry into the lung. G-CSF enhanced intrapulmonary bactericidal activity against this pathogen in normal and ethanol-treated rats. All intoxicated rats pretreated with the vehicle died, while >90% of rats pretreated with G-CSF survived. These findings suggest a potential role for G-CSF in mitigating the adverse effects of ethanol on PMNL delivery and pulmonary host defenses.