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Liver Int. 2006 Oct;26(8):1006-14.

Prevention of hepatic fibrosis in nonobese diabetic mice: a critical role for interferon-gamma.

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  • 1Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.

Abstract

BACKGROUND/AIMS:

Nonobese diabetic (NOD) mice, a model of type I diabetes mellitus, harbor certain unique defects in their immune system. The aim of this study was to investigate how NOD mice show hepatic injury and subsequent fibrogenic responses.

METHODS:

Hepatic fibrosis was induced by intraperitoneal injections of dimethylnitrosamine (DMN), and assessed biochemically and histologically. Expressions of cytokine messenger RNA (mRNA) in the liver were determined.

RESULTS:

In a model of liver cirrhosis induced by dimethylnitrosamine (DMN), we found that NOD mice had lower levels of hepatic fibrosis and better survival than control ICR mice. The resistance to DMN-induced lethality in NOD mice was independent of apoptosis and necrosis of hepatocytes, but apparently due to the prevention of hepatic fibrosis. We also found increased inductions of interferon-gamma (IFN-gamma) mRNA in the liver of NOD mice and of intracellular IFN-gamma from intrahepatic T cells following DMN administration. Treatment with neutralizing anti-IFN-gamma-antibody cancelled the inhibition of hepatic fibrosis in NOD mice.

CONCLUSIONS:

These results suggest that IFN-gamma is effective for inhibiting hepatic fibrosis and that genetic host factors may be important in determining differential responses to injury.

[PubMed - indexed for MEDLINE]
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