Role of the Kupffer cell in hepatic carcinogenesis in patients infected with hepatitis C virus

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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.