IL-18 plays an important role in the pathogenesis of autoinflammatory diseases, in particular in MAS or secondary hemophagocytic lymphohystiocitosis (sHLH) and sJIA/AOSD, but also in other monogenic autoinflammatory disorders that may be associated with high levels of IL-18, such as XIAP deficiency, NLRC4 gain-of-function disorders, or diseases associated with PSTPIP1 and MEVF mutations; however, in most patients with Familial Mediterranean fever (FMF), the serum levels of IL-18 are generally not significantly elevated [2,5,41]. This evidence concerns the gene NLRC4 and macrophage activation syndrome.