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 greater than 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.
Nelson
S
S
Department of Pulmonary Medicine, Louisiana State University Medical Center, New Orleans 70112.
Summer
W
W
Bagby
G
G
Nakamura
C
C
Stewart
L
L
Lipscomb
G
G
Andresen
J
J
D000435:Alcoholic Intoxication / Q000150:complications / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D007710:Klebsiella Infections / Q000517:prevention & control*; D007711:Klebsiella pneumoniae / Q000276:immunology; D008168:Lung / Q000276:immunology*; D008297:Male; D011014:Pneumonia / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000627:therapeutic use
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor