Premium
Alcohol Enhances Lipopolysaccharide‐Induced Increases in Nitric Oxide Production by Kupffer Cells Via Mechanisms Dependent on Endotoxin
Author(s) -
Enomoto Nobuyuki,
Ikejima Kenichi,
Kitamura Tsuneo,
Oide Hirosumi,
Takei Yoshiyuki,
Sato Nobuhiro,
Thurman Ronald G.
Publication year - 2000
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2000.tb00013.x
Subject(s) - lipopolysaccharide , kupffer cell , nitric oxide , sensitization , polymyxin b , ethanol , chemistry , gastrointestinal tract , pharmacology , endocrinology , medicine , microbiology and biotechnology , biochemistry , immunology , biology , antibiotics
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.