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Effect of Long‐Term Ethanol Consumption on Ability to Produce Cytokine‐Induced Neutrophil Chemoattractant‐1 in the Rat Liver and Its Gender Difference
Author(s) -
Yamada Shinwa,
Matsuoka Hirofumi,
Harada Yuji,
Momosaka Yasuhiro,
Izumi Hiroto,
Kohno Kimitoshi,
Yamaguchi Yasuo,
Eto Sumiya
Publication year - 1999
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.1530-0277.1999.tb04536.x
Subject(s) - chemokine , medicine , endocrinology , alcoholic hepatitis , cytokine , lipopolysaccharide , liver injury , spleen , ethanol , chemotaxis , monocyte , tumor necrosis factor alpha , neutrophile , alcoholic liver disease , biology , inflammation , receptor , biochemistry , cirrhosis
Gut‐derived lipopolysaccharide (LPS) may contribute to hepatocellular necrosis in alcoholic hepatitis through neutrophil sequestration in hepatic sinusoids. It is well known that the female has a greater susceptibility to alcoholic liver injury than the male. The aim of the present study was to investigate the effect of long‐term ethanol consumption on ability of the liver to produce cytokine‐induced neutrophil chemoattractant‐1 (CINC‐1), the most potent neutrophil‐chemokine in rats, after LPS administration. Furthermore, we aimed to evaluate the gender difference in this ability. Male and female rats were pair‐fed a liquid diet containing 36% of the total calories as ethanol or dextrose for 6 to 8 weeks. They were given LPS intravenously, and chemokine mRNA expression in the liver was evaluated after 2 and 6 hr. To study the organ or chemokine specificity, CINC‐1 mRNA expression in the spleen and monocyte chemoattractant protein (MCP)‐l mRNA level were also determined. Serum ALT activity started to increase between 2 and 6 hr. Female rats fed an ethanol diet showed significantly higher ALT activity 6 hr after LPS injection than the male rats. CINC‐1 mRNA expressions in the liver after 2 and 6 hr were significantly higher in the ethanol‐fed group, compared with the pair‐fed control. Female rats fed an ethanol diet showed a significantly higher level of CINC‐1 mRNA in the liver than the male rats 2 hr after LPS injection. CINC‐1 levels in the liver homogenates paralleled closely its mRNA expression, whereas its concentrations in sera did not correlate with those in the liver. Neither CINC‐1 mRNA expression in the spleen nor MCP‐1 mRNA expression in the liver was affected by ethanol feeding or gender. An additional experiment using the gonadectomized rats fed an ethanol diet showed that gonadectomy totally abolished the gender difference in CINC‐1 mRNA of the liver. We conclude that CINC‐1 induction in the liver may be responsible for LPS‐induced hepatitis in the ethanol‐fed rats, and that the difference in ability to produce CINC‐1 between males and females is one important factor that may partly account for the gender difference of alcoholic liver disease.