Murine Models of Secondary Cytokine Storm Syndromes

Abstract

Hemophagocytic lymphohistiocytosis (HLH) comprises a broad spectrum of life-threatening cytokine storm syndromes, classified into primary (genetic) or secondary (acquired) HLH. The latter occurs in a variety of medical conditions, including infections, malignancies, autoimmune and autoinflammatory diseases, acquired immunodeficiency, and metabolic disorders. Despite recent advances in the field, the pathogenesis of secondary HLH remains incompletely understood. Considering the heterogeneity of triggering factors and underlying diseases in secondary HLH, a large diversity of animal models has been developed to explore pivotal disease mechanisms. To date, over 20 animal models have been described that each recapitulates certain aspects of secondary HLH. This review provides a comprehensive overview of the existing models, highlighting relevant findings, discussing the involvement of different cell types and cytokines in disease development and progression, and considering points of interest toward future therapeutic strategies.

Keywords: Animal models; Autoimmunity/autoinflammation-associated; Cell types; Cytokine storm; Hemophagocytic lymphohistiocytosis (HLH); Infection-associated; Macrophage activation syndrome (MAS); Metabolic disorder-associated; Mouse models; Pathogenesis.