Clinically relevant concentrations of ethanol attenuate primed neutrophil bactericidal activity.
BACKGROUND
Acute alcohol intoxication is associated with an increased risk of infection in the injured patient. The impact of clinically relevant levels of ethanol (ETOH) on neutrophil (PMN) bactericidal activity remains ill-defined. PMN priming optimizes microbicidal activity by enhancing oxygen radical production, degranulation, and adhesion molecule up-regulation. We hypothesized that clinically relevant levels of ETOH attenuate these primed PMN responses critical to eradicate infection.


METHODS
After incubation with ETOH (0-1.0%), isolated human PMNs were primed with beta-acetyl-gamma-O-alkyl and activated with N-formyl-methionyl-leucyl-phenylalanine. Superoxide generation was measured by cytochrome c reduction, elastase release was measured by cleavage of methoxysuccinyl-ala-ala-pro-val-p-nitroanilide, and CD11b was measured by fluorescent monoclonal antibody staining. Bactericidal activity was assessed by Staphylococcus aureus killing.


RESULTS
ETOH attenuated superoxide production dose-dependently with significance at 0.3% ETOH. Elastase release was attenuated starting at 0.2% ETOH, and CD11b expression was reduced starting at 0.4% ETOH. S. aureus killing was impaired dose-dependently with significance at 0.3% ETOH.


CONCLUSIONS
Clinically relevant concentrations of ETOH attenuate PMN functions critical in host defense against invading pathogens. These results provide direct in vitro evidence consistent with previous in vivo data that acute alcohol intoxication is important in the pathogenesis of trauma-related infections.
Tamura
D Y
DY
Department of Surgery, Denver Health Medical Center, Colorado 80204, USA.
Moore
E E
EE
Partrick
D A
DA
Johnson
J L
JL
Offner
P J
PJ
Harbeck
R J
RJ
Silliman
C C
CC
D000435:Alcoholic Intoxication / Q000276:immunology; D001770:Blood Bactericidal Activity / Q000187:drug effects*; D002478:Cells, Cultured; D000431:Ethanol / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D019272:Leukocyte Elastase / Q000096:biosynthesis; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation
D016177:Macrophage-1 Antigen; D013481:Superoxides; D000431:Ethanol; D019272:Leukocyte Elastase