Effect of alcohol on the secretion of tumor necrosis factor-alpha by macrophages in the presence of rat serum.
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 determine the pathophysiological roles of macrophages in alcoholic liver disease, we examined the effect of ethanol on TNF-alpha secretion of rat Kupffer cells, alveolar macrophages, and peritoneal macrophages in the presence or absence of LBP.


METHODS
Kupffer cells, alveolar macrophages, and peritoneal macrophages were isolated from male Sprague Dawley rats. After the preculture in the medium containing 0, 10, 50, and 100 mmol/liter of ethanol, TNF-alpha secretion by these cells incubated with 100 ng/ml of endotoxin in the presence or absence of LBP (1% rat serum) was determined.


RESULTS
In the absence of LBP, an addition of ethanol to the medium suppressed TNF-alpha secretion of alveolar macrophages. Kupffer cells and peritoneal macrophages were less affected. Addition of LBP led to marked enhancement (7- to 24-fold) of TNF-alpha secretion of macrophages either with or without ethanol in the medium. Although ethanol tended to suppress TNF-alpha secretion of these cells, alveolar macrophages were less affected in the presence of LBP.


CONCLUSIONS
Serum LBP enhances the secretion of TNF-alpha by macrophages. Alveolar macrophages may be important for excessive production of TNF-alpha in chronic alcoholics with endotoxemia.
Third Department of Internal Medicine, Nara Medical University, Kashihara-shi, Japan. ynktn@gyoumeikan.or.jp
Yoshihiro
Y
Nakatani
Hiroshi
H
Fukui
Toshiyuki
T
Kitazawa
Masao
M
Fujimoto
Junichi
J
Yamao
Masahito
M
Uemura
D000209:Acute-Phase Proteins; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D007728:Kupffer Cells / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008108:Liver Diseases, Alcoholic / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D000431:Ethanol; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein