Granulocyte colony-stimulating factor modulates the pulmonary host response to endotoxin in the absence and presence of acute ethanol intoxication.
Alcohol impairs neutrophil function and predisposes the host to infectious complications. Granulocyte colony-stimulating factor (G-CSF) increases both the number and functional activities of neutrophils. This study investigated the effects of G-CSF on the pulmonary response to endotoxin in rats with or without acute ethanol intoxication. Acute ethanol intoxication inhibited tumor necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-2 production in the lung and suppressed the recruitment of neutrophils into the lung. Ethanol also inhibited CD11b/c expression on recruited neutrophils and suppressed the phagocytic activity of circulating neutrophils. G-CSF pretreatment up-regulated CD11b/c expression on circulating polymorphonuclear leukocytes, augmented the recruitment of neutrophils into the lung, and enhanced the phagocytic activity of circulating and recruited neutrophils in both the absence and presence of acute ethanol intoxication. G-CSF inhibited MIP-2 but not TNF-alpha production in the lung. These data suggest that G-CSF may be useful in the prevention or treatment of infections in persons immunocompromised by alcohol.
Zhang
P
P
Department of Medicine, Section of Pulmonary/Critical Care, and Alcohol Research Center, Louisiana State University Medical Center, New Orleans, LA 70112, USA. pzhang@lsumc.edu.
Bagby
G J
GJ
Stoltz
D A
DA
Summer
W R
WR
Nelson
S
S
D000208:Acute Disease; D000435:Alcoholic Intoxication / Q000276:immunology*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D054426:Chemokine CXCL2; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000187:drug effects; D008297:Male; D015846:Monokines / Q000096:biosynthesis; D009504:Neutrophils / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015815:Cell Adhesion Molecules; D054426:Chemokine CXCL2; D004731:Endotoxins; D008070:Lipopolysaccharides; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; C044101:endotoxin, Escherichia coli; D006861:Hydrogen Peroxide