Alcohol enhances lipopolysaccharide-induced increases in nitric oxide production by Kupffer cells via mechanisms dependent on endotoxin.
BACKGROUND
Ethanol causes both tolerance and sensitization of Kupffer cells. Accordingly, this study examines the effect of acute ethanol consumption on nitric oxide (NO) production from Kupffer cells with or without lipopolysaccharide (LPS) treatment.


METHODS
Rats were given ethanol (4 g/kg body weight) intragastrically, and Kupffer cells were isolated 2 and 24 hr later. Some rats were treated for 4 days with 150 mg/kg/day of polymyxin B and 450 mg/kg/day of neomycin to prevent growth of intestinal bacteria, the primary source of endotoxin in the gastrointestinal tract. After addition of LPS, NO was measured by the Griess reaction.


RESULTS
Two hours after ethanol administration, LPS-induced NO production by Kupffer cells was diminished by 50% but was enhanced 2-fold at 24 hr. Sterilization of the gut with antibiotics blocked this enhancement.


CONCLUSIONS
Kupffer cells isolated from rats early after ethanol exhibited tolerance to LPS, whereas sensitization was observed later. It is likely that sensitization to Kupffer cell is caused by gut-derived endotoxin.
Enomoto
N
N
Laboratory of Hepatobiology and Toxicology, University of North Carolina at Chapel Hill, 27599-7365, USA.
Ikejima
K
K
Kitamura
T
T
Oide
H
H
Takei
Y
Y
Sato
N
N
Thurman
R G
RG
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D000431:Ethanol