In yet another mouse model, upon repeated TLR9 stimulation, IL-18BP knockout mice showed severe MAS manifestations, including increased weight loss, splenomegaly, anemia, thrombocytopenia, hyperferritinemia, and bone marrow hemophagocytosis, as well as elevated circulating free IL-18 levels, higher IFN-γ production, and enhanced IFN-γ molecular signature. This evidence concerns the gene IFNG and macrophage activation syndrome.