Interleukin 18 binding protein (IL-18BP) is a physiological inhibitor that acts through binding to the receptor-binding site of IL-18. IL-18 stimulates INF-γ, which then stimulates 18BP production via NF-κB. The interaction between IL-18 and IL-18BP has a significant role in the inflammation process. IL-18 BPs have four isoforms, a, b, c and d, which are spliced by different ways. The IL-18 BP isoforms a and c each contain one immunoglobulin (Ig)-like C2-type domain which is essential to the binding and neutralizing properties of the binding proteins. The IL-18 BP isoforms b and d lack a complete Ig domain. The expression of IL-18 and the IL-18BP are indentified in immune tissues such as the spleen, but also in nonimmune cells including keratinocytes.