Our data suggest that, whilst the NLRP3 inflammasome is responsible for increased blood circulation levels of IL-18 in MAS, it is not responsible for the development of other features of MAS pathogenesis in CpG-induced MAS, such as hyperferritinaemia and splenomegaly, and therefore, indicate that alternative mechanisms are responsible for the splenomegaly, hypercytokinaemia and organ dysfunction in MAS. Here, IL18 is linked to macrophage activation syndrome.