| Project/Area Number |
06670578
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Nara Medical University |
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Principal Investigator |
FUKUI Hiroshi Nara Medical University, 3rd Dept of Internal Medicine, Professor, 医学部, 教授 (80145838)
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| Co-Investigator(Kenkyū-buntansha) |
UEMURA Masahito Nara Medical University, 3rd Dept of Internal Medicine, Lecturer, 医学部, 講師 (90151836)
KIKUCHI Eiryou Nara Medical University, 3rd Dept of Internal Medicine, Lecturer, 医学部, 講師 (50214747)
辻井 正 奈良県立医科大学, 医学部, 教授 (30075064)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | endotoxin / albumin / high density lipoprotein (HDL) / alcohol / acute hepatic failure / tumor necrosis factor (TNF) / トランスフェリン / TNF-α / IL-6 / G-CSF |
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| Research Abstract |
Significance of endotoxin (Et) binding proteins in severe liver disturbance was investigated in clinical and experimental studies. Clinical studies : In the present study, we confirmed that serum albumin has Et binding and Et inactivating actions. There was a decrease in Et inactivating rate (EIR) in terminal liver cirrhosis. EIR was positively correlated to serum HDL-cholesterol level and Et binding capacity of albumin and negatively correlated to Et binding capacity of transferrin in liver cirrhosis. In patients with advanced cirrhosis, plasma interleukin (IL) -1beta, IL-6 and tumor necrosis factor (TNF) -alpha levels were increased, which was related to decreased Et binding capacity of albumin. These data suggested that decreased Et inactivation by albumin may lead to augmentatin of endotoxicity and elevations of the above cytokines. Experimental studies : The hepatic production of Et binding protein was increased when the Kupffer cells were preincubated in the medium containing ethanol and the resultant culture supernatant was added to the hepatocyte culture system. The amount of Et binding protein produced by the hepatocytes was increased as the ethanol concentration in the culture medium of Kupffer cells was increased. This endotoxin binding protein was proved to enhance the uptake of endotoxin and to suppress the production of TNF by the Kupffer cells. In acute ethanol-loaded rats, albumin-bound and highdensity lipoprotein (HDL) -bound Et was markedly increased. In chronic ethanolloaded rats, HDL-bound Et was increased. In the chronic ethanol-fed rats with an additional 5g/kg bw of ethanol load, blood TNF and ALT levels were increased, when the HDL-bound Et was not further increased. In vitro study revealed that albumin and HDL inhibited Et uptake and TNF production by Kupffer cells. These data suggest that albumin and HDL may act as Et binding proteins and attenuate endotoxicity in alcoholics.
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