The Multifaceted Immunology of Cytokine Storm Syndrome

Cytokine storm syndromes (CSSs) are poten-tially fatal hyperinflammatory states that share the underpinnings of persistent immune cell activation and uninhibited cytokine production. CSSs can be genetically determined by inborn errors of immunity (i.e., familial hemophagocytic lymphohistiocytosis) or develop as a complica-tion of infections, chronic inflammatory diseases (e.g., Still disease), or malignancies (e.g., T cell lymphoma). Therapeutic interventions that acti-vate the immune system such as chimeric Ag receptor T cell therapy and immune check-point inhibition can also trigger CSSs in the setting of cancer treatment. In this review, the biology of different types of CSSs is explored, and the current knowledge on the involve-ment of immune pathways and the contribu-tion of host genetics is discussed. The use of animal models to study CSSs is reviewed, and their relevance for human diseases is discussed. Lastly, treatment approaches for CSSs are dis-cussed with a focus on interventions that target immune cells and cytokines.

Automated summary

Cytokine storm syndromes (CSSs) are potentially fatal hyperinflammatory states characterized by persistent immune cell activation and excessive cytokine production. CSSs can be caused by genetic errors of immunity, infections, chronic inflammatory diseases, or malignancies. This review explores the biology of different types of CSSs, the involvement of immune pathways, the contribution of host genetics, and discusses treatment approaches.