Review Article

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

Christopher Johnson, Yuyan Han, Nathan Hughart, Jennifer McCarra, Gianfranco Alpini, Fanyin Meng


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.