Dose-dependent effect of ethanol on hepatic oxidative stress and interleukin-6 production after burn injury in the mouse.
BACKGROUND
Burned patients with detectable blood alcohol levels (BAL) show an elevated mortality rate. Interleukin (IL)-6 and reactive oxygen species (ROS) production is stimulated independently by alcohol and burn injury. The aim of the study was to determine whether increasing levels of alcohol differentially enhance the hepatic production of IL-6 and ROS after burn in a murine model of dorsal scald injury. Groups of mice received either saline or alcohol intraperitoneally to reach a BAL of 100 mg/dl or 300 mg/dl at the time of burn (15% total body surface scald) or sham injury.


RESULTS
Burn injury alone resulted in a low mortality rate at 24 hr after injury as did the burn group with a BAL of 100 mg/dl (15%), whereas 57% of the mice burned with a BAL of 300 mg/dl did not survive (p = 0.02). Twenty-four hours after burn or sham injury, IL-6 levels were measured by enzyme-linked immunosorbent assay in serum and liver. In the saline-treated group, IL-6 circulating and hepatic levels rose after burn injury (p < 0.03). Circulating IL-6 levels in sham mice increased 1.5-fold in the group with a BAL of 100 mg/dl and 3-fold in those with a BAL of 300 mg/ml (p = 0.005 versus burn-injured, saline-treated). IL-6 hepatic production after burn injury was higher in the mice with a BAL of 300 mg/dl than in those with a BAL of 100 mg/dl and the saline-treated group (p = 0.001). Among the burned mice, alcohol exposure increased hepatic ROS production, measured by lipid peroxidation and protein oxidation, in a dose-dependent manner.


CONCLUSIONS
Alcohol enhances in a dose-dependent manner the hepatic production of IL-6 induced by burn injury through the modulation of oxidative stress. The increased mortality rate of mice exposed to alcohol and burn injury may be due to the adverse effect on immune function induced by IL-6 elevation.
Colantoni
A
A
Division of Gastroenterology and Hepatology, Loyola University Chicago, Maywood, Illinois 60153, USA. acolan@lumc.edu
Duffner
L A
LA
De Maria
N
N
Fontanilla
C V
CV
Messingham
K A
KA
Van Thiel
D H
DH
Kovacs
E J
EJ
D000818:Animals; D002056:Burns / Q000276:immunology / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000008:administration & dosage* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism
D002492:Central Nervous System Depressants; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D000431:Ethanol