Among innate proinflammatory cytokines, IL-18 has attracted increasing attention as a key mediator in autoinflammatory diseases associated with the development of macrophage activation syndrome (MAS) including systemic juvenile idiopathic arthritis (16–25), adult-onset Still’s disease (26–30), XIAP deficiency (31, 32), NLRC4 gain of function (8, 33), neonatal onset of cytopenia, autoinflammation, rash, and episodes of hemophagocytic lymphohistiocytosis (NOCARH syndrome) (34) and purine nucleoside phosphorylase (PNP)-deficiency (35). This evidence concerns the gene NLRC4 and macrophage activation syndrome.