The production of tumor necrosis factor-alpha by macrophages in rats with acute alcohol loading.
BACKGROUND
It is suggested that endotoxin, proinflammatory cytokines, and lipopolysaccharide-binding protein (LBP) play an important role in the development of alcoholic liver disease. Our previous study showed that splenic macrophages were important for endotoxin uptake and excessive production of tumor necrosis factor (TNF) in rats given large amounts of alcohol. To study the pathophysiological roles of macrophages in alcoholic liver diseases, we examined the production of TNF-alpha by rat Kupffer cells, splenic macrophages, and alveolar macrophages with acute alcohol loading in the presence or absence of LBP.


METHODS
Kupffer cells, splenic macrophages, and alveolar macrophages were isolated from male Wistar rats given 5 mg/g body weight of ethanol intraperitoneally after an hour. The production of TNF-alpha by these cells incubated with endotoxin 100 ng/ml in the presence or absence of LBP (1% rat serum) was determined.


RESULTS
Acute alcohol loading did not affect the production of TNF-alpha by Kupffer cells. With acute alcohol loading, splenic macrophages tended to produce more TNF-alpha. Alveolar macrophages produced more TNF-alpha than Kupffer cells, and although the production of TNF-alpha by alveolar macrophages tended to be suppressed by acute alcohol loading, the production of TNF-alpha by alveolar macrophages still remained high in the presence of rat serum.


CONCLUSIONS
Splenic macrophages and alveolar macrophages may be related to excessive production of TNF-alpha in acute alcoholics with endotoxemia.
Kitazawa
Toshiyuki
T
Third Department of Internal Medicine, Nara Medical University, Kashihara-shi, Nara, Japan.
Nakatani
Yoshihiro
Y
Fujimoto
Masao
M
Tamura
Nobuhiro
N
Uemura
Masahito
M
Fukui
Hiroshi
H
D000435:Alcoholic Intoxication / Q000276:immunology*; D000818:Animals; D004926:Escherichia coli / Q000276:immunology; D007728:Kupffer Cells / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha