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Effect of Alcohol on the Secretion of Tumor Necrosis Factor‐α by Macrophages in the Presence of Rat Serum
Author(s) -
Nakatani Yoshihiro,
Fukui Hiroshi,
Kitazawa Toshiyuki,
Fujimoto Masao,
Yamao Junichi,
Uemura Masahito
Publication year - 2002
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.1530-0277.2002.tb02708.x
Subject(s) - tumor necrosis factor alpha , secretion , lipopolysaccharide , proinflammatory cytokine , alcoholic liver disease , endocrinology , medicine , macrophage , kupffer cell , lipopolysaccharide binding protein , inflammation , chemistry , immunology , in vitro , biochemistry , acute phase protein , cirrhosis
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‐α 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‐α 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‐α 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‐α secretion of macrophages either with or without ethanol in the medium. Although ethanol tended to suppress TNF‐α secretion of these cells, alveolar macrophages were less affected in the presence of LBP. Conclusions Serum LBP enhances the secretion of TNF‐α by macrophages. Alveolar macrophages may be important for excessive production of TNF‐α in chronic alcoholics with endotoxemia.