IL-18

Interleukin 18 (IL-18) is a 193 amino acid glycoprotein with a mass of 22.3 kDa. IL-18 is part of the IL-1 family; it has structural similarity to IL-1beta and is activated from a pro-form by intracellular IL-1beta converting enzyme (ICE). IL-18 receptor (IL-18R) is part of the toll-like receptor family, and IL-18 activity can be neutralized by IL-18-binding protein (IL-18bp). IL-18 plays a major role in Th1-mediated immune response in collaboration with IL-12. Endogenous functions of IL-18 include stimulation of IFN-y production, increase in cytotoxicity of natural killer cells, stimulation of T helper cell differentiation and NF-kB release. IL-18 plays a major role in stimulating natural killer cell function during viral and bacterial infections. IL-18 is up-regulated and thought to play a major inflammatory role in gastrointestinal cancers. IL-18 serum concentrations correlate to patient tumor malignancies in individuals with breast cancer. IL-18 is a sensitive tumor marker in oral cavity cancer patients and increasing serum levels of the marker have been observed along the progression of the disease. This relationship is also thought to involve VEGF6. IL-18 has been found to increase expression of vascular cellular adhesion molecule 1 (VCAM-1) in hepatic melanoma which increases tumor adherence and metastasis. IL-18 has been proposed as a novel adjuvant therapy against cancer.