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 re levant levels of ethanol (ETOH) on neutrophil (PMN) bactericidal activ ity remains ill-defined. PMN priming optimizes microbicidal activity b y enhancing oxygen radical production, degranulation, and adhesion mol ecule up-regulation, We hypothesized that clinically relevant levels o f ETOH attenuate these primed PMN responses critical to eradicate infe ction. Methods: After incubation with ETOH (0-1.0%), isolated human PM Ns were primed with beta-acetyl-gamma-O-alkyl and activated with N-for myl-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 measu red by fluorescent monoclonal antibody staining. Bactericidal activity was assessed by Staphylococcus aureus killing. Results: ETOH attenuat ed superoxide production dose-dependently with significance at 0.3 % E TOH. Elastase release was attenuated starting at 0.2% ETOH, and CD11b expression was reduced starting at 0.4% ETOH. S. aureus killing was im paired dose-dependently with significance at 0.3% ETOH. Conclusion: Cl inically relevant concentrations of ETOH attenuate PMN functions criti cal in host defense against invading pathogens. These results provide direct in vitro evidence consistent with previous in vivo data that ac ute alcohol intoxication is important in the pathogenesis of trauma-re lated infections.