title: Clinically relevant concentrations of ethanol attenuate primed neutrophil bactericidal activity.
abstract: 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.
authors.affiliation: Department of Surgery, Denver Health Medical Center, Colorado 80204, USA.
authors.forename: D Y
authors.initials: DY
authors.lastname: Tamura
authors.forename: E E
authors.initials: EE
authors.lastname: Moore
authors.forename: D A
authors.initials: DA
authors.lastname: Partrick
authors.forename: J L
authors.initials: JL
authors.lastname: Johnson
authors.forename: P J
authors.initials: PJ
authors.lastname: Offner
authors.forename: R J
authors.initials: RJ
authors.lastname: Harbeck
authors.forename: C C
authors.initials: CC
authors.lastname: Silliman
mesh_terms: 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
chemical_list: D016177:Macrophage-1 Antigen; D013481:Superoxides; D000431:Ethanol; D019272:Leukocyte Elastase