Relationship between interleukin‐6 and proliferation and differentiation in cholangiocarcinoma

AIMS: Interleukin-6 (IL-6) has been implicated as a mediator of growth control in several human neoplasms. The significance of IL-6 expression in human cholangiocarcinoma was examined in this study. METHODS AND RESULTS: IL-6 expression was examined in 43 surgically resected cholangiocarcinomas and a cholangiocarcinoma cell line CCKS1, derived from abdominal metastasis of moderately differentiated adenocarcinoma, by immunohistochemical and in-situ hybridization techniques. In non-neoplastic bile ducts, IL-6 was constitutively but weakly expressed. In surgical cases of cholangiocarcinoma, IL-6 was frequently and strongly expressed in the cytoplasm of well-differentiated cholangiocarcinoma, while its expression was decreased, and less intense or absent in moderately and poorly differentiated areas, respectively. IL-6 mRNA was detected in the cytoplasm of carcinoma cells of two cases of cholangiocarcinomas positive for IL-6. IL-6 was detected in hepatic bile from two cholangiocarcinoma cases studied. The proliferation antigen Ki67 was found to be more frequently expressed in IL-6 negative carcinoma cells than in IL-6 positive carcinoma cells (P < 0.01). In cultured carcinoma cells line CCKS1, IL-6, IL-6 mRNA and IL-6 receptor alpha chain were detected in the cytoplasm of carcinoma cells, suggesting an autocrine effect of IL-6 on carcinoma cells. CONCLUSION: IL-6 expression is inversely related to cell proliferation and positively related to differentiation in cholangiocarcinoma.