Interleukin-6 and its receptor, key players in hepatobiliary inflammation and cancer.

In recent years, the relationship between interleukin-6 (IL-6), hepatobiliary inflammation, and cancer has been studied. It is becoming clear that this cytokine plays an important role in the pathogenesis of both cholangiocarcinoma (CCA, cancer of the bile ducts) and hepatocellular carcinoma (HCC, cancer arising from the liver parenchyma). Inflammation due to various chronic hepatobiliary diseases including hepatitis B, hepatitis C, alcoholic liver injury, and primary sclerosing cholangitis (PSC) has been associated with increased levels of IL-6 and with increased rates of malignancy. In this review, we will summarize the current knowledge linking inflammation to hepatobiliary cancer, and discuss the key role of IL-6 and its signaling pathways in mediating this link. We will first review the major signaling pathways that are triggered when IL-6 engages its receptor. These include PI3 kinase, JAK/STAT, p38 MAP kinase and others that ultimately lead to cell proliferation, protection from apoptosis and increased metastatic potential. We will then discuss data linking IL-6 and hepatobiliary cancer, namely HCC and CCA.