Murine models of cytokine storm syndrome. Primary HLH can be modeled by infecting mice with deficiency of PRF1, RAB27A, UNC13D, and STX11 with LCMV. Manifestations of MAS can be induced in WT mice or IL-6 transgenic mice using TLR ligands. Constitutive activation of the metabolic regulator mTORC1 by conditional deletion of Tsc2 is also shown to trigger an MAS-like disease. The typical timeline of disease development and key manifestations of MAS are displayed for each model. Abbreviations: CpG, 5'—Cytosine—phosphate—Guanine—3'; HLH, hemophagocytic lymphohistiocytosis; HSP, hepatosplenomegaly; LPS, lipopolysaccharide; MAS, macrophage activation syndrome; poly I:C, polyinosinic-polycytidylic acid; sCD25, soluble IL-2 receptor-α.