GRANULOCYTE COLONY-STIMULATING FACTOR ENHANCES PULMONARY HOST DEFENSES IN NORMAL AND ETHANOL-TREATED RATS

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 of PMNL, the effect of G-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.