Table 2.

Immunologic therapeutics used in treatment of cytokine storm syndrome

Therapeutic agent	Target	Mechanism of action	Application
Etoposide (topoisomerase II inhibitor)	T lymphocytes	Inhibits cell proliferation	HLH
Almetuzumab (anti-CD52)	Lymphocytes, monocytes	Depletes leukocytes	HLH
Rituximab (anti-CD20 mAb)	B lymphocytes	Depletes B lymphocytes	EBV-MAS
Anti-thymocyte globulin (ATG)	T lymphocytes	Depletes T lymphocytes	HLH
Cyclosporin A (calcineurin inhibitor)	IL-2, IFN-γ, others	Inhibits cell proliferation and effector functions	HLH, MAS
Anakinra (rhIL-1Ra)	IL-1	Blocks IL-1 from receptor binding	MAS, CRS
Tocilizumab (anti-IL-6R mAb)	IL-6	Blocks IL-6 from receptor binding	MAS, CRS
Emapalumab (anti-IFN-γ mAb)	IFN-γ	Neutralizes IFN-γ	HLH, MAS
Tadekinig alfa (rhIL-18BP)	IL-18	Blocks IL-18 from receptor binding	NLRC4-MAS, XIAP
Ruxolitinib (JAK1/2 inhibitor)	IFN-γ, IL-6, IL-12, others	Inhibits cytokine signaling	HLH, MAS, severe COVID-19
Plasmapheresis	Multiple cytokines	Remove proinflammatory mediators	severe COVID-19
Dexamethasone (glucocorticoids)	Multiple cytokines	Broad immunosuppression	Most CSS
Intravenous immunoglobulin (IVIG)	Multiple cytokines	unknown	MAS, MIS-C

Abbreviations: BP, binding protein; COVID-19, coronavirus disease of 2019; CRS, cytokine release syndrome; EBV, Epstein-Barr virus; HLH, hemophagocytic lymphohistiocytosis; IFN, interferon; JAK, Janus kinase; mAb, monoclonal antibody; MAS, macrophage activation syndrome; MIS-C, multisystem inflammatory syndrome in children; NLRC4, NOD-like receptor family CARD domain containing 4; Ra, receptor antagonist; rh, recombinant human; XIAP, X-linked inhibitor of apoptosis protein.