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Interleukin-18 is a member of the interleukin-1 family of cytokines with pro-inflammatory and tumor-suppressive properties. Its ability to potently enhance the production of interferon-gamma indicates in particular the crucial function of interleukin-18 as an immunomodulatory molecule. In fact, high levels of interleukin-18 are detected in human diseases associated with immunoactivation including viral or bacterial infections and chronic inflammation. Animal models suggest suppression of interleukin-18 bioactivity as a novel therapeutic concept specifically for the treatment of chronic inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis. It is the only cytokine with a unique capacity to induce T helper 1 or T helper 2 polarization, depending on the immunologic context.