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Clinically relevant concentrations of ethanol attenuate primed neutrophil bactericidal activity
D Y Tamura1, E E Moore, D A Partrick
1Department of Surgery, Denver Health Medical Center, Colorado 80204, USA.
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.
Conclusion:
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.
Insights
Acute alcohol intoxication impairs neutrophil function, reducing the body's ability to fight Staphylococcus aureus infections. This study shows how ethanol affects key immune responses in neutrophils.
Area of Science:
- Immunology
- Toxicology
- Infectious Diseases
Background:
- Acute alcohol intoxication is linked to higher infection risks in trauma patients.
- The effect of ethanol on neutrophil bactericidal activity is not well understood.
- Neutrophil priming enhances immune responses against pathogens.
Purpose of the Study:
- To investigate how clinically relevant ethanol levels impact primed neutrophil function.
- To determine the effect of ethanol on neutrophil-mediated killing of Staphylococcus aureus.
Main Methods:
- Human neutrophils were exposed to varying ethanol concentrations (0-1.0%).
- Neutrophil priming and activation were performed using specific reagents.
- Superoxide production, elastase release, CD11b expression, and Staphylococcus aureus killing were measured.
Main Results:
- Ethanol significantly reduced superoxide production, elastase release, and CD11b expression in a dose-dependent manner.
- Neutrophil-mediated killing of Staphylococcus aureus was significantly impaired at 0.3% ethanol.
- These effects were observed at clinically relevant ethanol concentrations.
Conclusions:
- Clinically relevant ethanol concentrations attenuate critical neutrophil functions for host defense.
- In vitro findings support in vivo data linking alcohol intoxication to trauma-related infections.
- Ethanol directly impairs neutrophil bactericidal activity, increasing infection susceptibility.