| Project/Area Number |
13671293
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | University of Yamanashi, Faculty of Medicine |
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Principal Investigator |
KONO Hiroshi University of Yamanashi, Faculty of Medicine, Research Associate, 医学部, 助手 (40322127)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Hideki University of Yamanashi, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30181316)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Hepatocellular Carcinoma / Oxidative stress / Kupffer cell / Interleukin-18 / Tumor immune system in the liver / Chronic Hepatitis C |
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| Research Abstract |
The number of Kupffer cells increased in the liver with hepatitis C virus infection. Alternatively, IL-18 is a pro-inflammatory cytokine and also a strong enhancer of anti-tumor immune system by activating lymphocytes. Since, IL-18 is predominantly produced by macrophage and the Kupffer cell is a predominant cell population of macrophages in the liver. Therefore, relationship between serum IL-18 level and population of the Kupffer cell in HCV infected patients with or without HCC was investigated.
Chronic liver disease (CLD) patients with anti-HCV antibody including chronic hepatitis and liver cirrhosis, patients bearing HCV related HCC, and healthy HCV negative subjects were included in this study. Serum IL-18, IL-12 levels were measured by ELISA. Messenger RNA expression of IL-1 and interferon (IFN)-γ was measured in the liver tissue by RT-PCR. Immunohistochemistry using IL-18 and CD68 anti-macrophage antibodies were performed in the liver. Moreover, oxidative stress marker 8-OHdG, HNE was assessed by immunohistochemistry and immuno-blotting in the liver.
Serum IL-18 and IL-12 level in CLD patients was significantly greater than other groups. Messenger RNA expression of Th1 cytokines was increased in the CLD patients. Immunohistochemistry was revealed that IL-18 positive cell was morphologically identified as the Kupffer cell. The number of CD68 positive cell was positively correlated with serum IL-18 levels and 8-OHdG expressions in the liver. Furthermore, after curative treatment of HCC, the disease free survival was significantly poor in the high IL-18 of 8-OHdG group.
In conclusion, increases in the number of the Kupffer cell and serum IL-18 levels could be involved in the progression of HCC. Furthermore, serum IL-18 level is practical to predict the high-risk group of HCC occurrence.
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