Significance of inflammatory mediators in hepatocellular carcinoma

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Aim and Purpose : Endogenous cannabinoids (CBs) have been confirmed to play a role as early mediators, while high mobility group box-1 (HMGB-1) is known to be a late mediator in inflammatory response with inducing various physiologic actions. The aim of this study is to clarify a relationship between various inflammatory mediators including cytokines for the development and progression of HCC. Patients and Methods : For patients with hepatocellular carcinoma (HCC:n=45), liver cirrhosis (LC:n=23) or chronic hepatitis (CH:n=10) as well as in healthy volunteers (HV, n=34), the serum levels of CBs, 2-arachidonoylglycerol (2-AG) and anandamide (AEA) were measured by high performance liquid chromatography combined mass spectrometry (LC/MS). The serum levels of HMGB-1 and 6 inflammatory cytokines were measured by an enzyme-linked immunosorbent assay (HV:n=10, CH:n=5, LC:n=7, HCC:n=17). The expression of receptors for CBs. CBIR and CB2R as well as receptor for advanced glycation end product (RAGE) were examined by immunohistochemical analyses using the resected samples of HCC (n=23). Results : In patients with HCC, the mean level of 2-AG was 15.92 ± 7.30 ng/ml, which was significantly higher than those of the other groups (p< 0.01). The serum level of IL-8 was significantly higher in the advanced HCC group (p< 0.01). The mean level of HMGB-1 in HCC group was 5.51±2.92 ng/ml, which was significantly higher than those of the other groups (p <0.01). There existed a significant correlation between 2-AG and HMGB-1 (r=0.872, P< 0.01). In the immunohistochemical analysis of I-ICC, the expressions of CB1R and RAGE correlated with dedifferentiation of HCC. Conclusions : 2-AG, CBIR, IL-8 and FIMGB-1 seem to be associated with the development and progression of HCC. Blockade of such mediators may have potential for prevention and treatment of HCC.