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Murine Models of Secondary Cytokine Storm Syndromes

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Cytokine Storm Syndrome

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. Currently, nearly 20 animal models have been described, each recapitulating 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 towards future therapeutic strategies.

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Abbreviations

Ag:

Antigen

APC:

Antigen-presenting cell

BP:

Binding protein

CAEBV:

Chronic active EBV infection

CCL:

C-C motif chemokine ligand

CFA:

Complete Freund’s adjuvant

CSS:

Cytokine Storm Syndrome

dsDNA:

Double-stranded DNA

EBV:

Epstein–Barr virus

GM-CSF:

Granulocyte macrophage colony stimulating factor

HIF:

Hypoxia-inducible factor

HLH:

Hemophagocytic lymphohistiocytosis

HSC:

Hematopoietic stem cell

HVP:

Herpesvirus papio

IDO:

Indoleamine 2,3-dioxygenase

IFN:

Interferon

IL:

Interleukin

IL2R:

IL-2 receptor

IRF:

Interferon-regulatory factor

IVIG:

Intravenous immunoglobulins

JAK:

Janus kinase

KO:

Knockout

LCMV:

Lymphocytic choriomeningitis virus

LPS:

Lipopolysaccharide

MAS:

Macrophage activation syndrome

MCMV:

Mouse cytomegalovirus

MHC:

Major histocompatibility complex

MMP:

Matrix metalloproteinase

NF-κB:

Nuclear factor κB

NK cell:

Natural killer cell

NOD:

Nonobese diabetic

NRG:

NOD/RAG/IL2Rγnull

NSG:

NOD/SCID/IL-2Rγ−/−

PBMC:

Peripheral blood mononuclear cell

pHLH:

Primary HLH

PPAR:

Peroxisome proliferator activated receptor

R:

Receptor

RAG:

Recombination-activating gene

RBC:

Red blood cell

sCD25:

Soluble CD25

SCF:

Stem cell factor

SCID:

Severe combined immunodeficient

sHLH:

Secondary HLH

sJIA:

Systemic juvenile idiopathic arthritis

SLE:

Systemic lupus erythematosus

STAT:

Signal transducer and activator of transcription

Tg:

Transgenic

Th:

T helper cell

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

Treg:

Regulatory T cell

WT:

Wild-type

YFP:

Yellow fluorescent protein

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Authors and Affiliations

  1. Laboratory of Immunobiology, Rega Institute, KU Leuven, Leuven, Belgium

    Ellen Brisse, Carine H. Wouters & Patrick Matthys

  2. Department of Pediatric Rheumatology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium

    Carine H. Wouters

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  1. Ellen Brisse
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  2. Carine H. Wouters
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Correspondence to Patrick Matthys .

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  1. UAB School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Randy Q. Cron

  2. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Edward M. Behrens

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Brisse, E., Wouters, C.H., Matthys, P. (2019). Murine Models of Secondary Cytokine Storm Syndromes. In: Cron, R., Behrens, E. (eds) Cytokine Storm Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-030-22094-5_29

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