IL-1α, IL-1β, and IL-18 are also central pathogenic mediators in MAS (Miettunen et al. 2011; Shigemura et al. 2011) and all these three molecules are released during pyroptosis, which likewise is an important pathway for HMGB1 release (Lamkanfi et al. 2010; Lu et al. 2012). This evidence concerns the gene IL18 and macrophage activation syndrome.