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Review
. 2020 Dec 3;383(23):2255-2273.
doi: 10.1056/NEJMra2026131.

Cytokine Storm

Affiliations
Review

Cytokine Storm

David C Fajgenbaum et al. N Engl J Med. .
No abstract available

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Figures

Figure 1
Figure 1. Clinical Presentation of Cytokine Storm.
A wide range of clinical and laboratory abnormalities can be observed in cytokine storm. However, all cases involve elevated circulating cytokine levels, acute systemic inflammatory symptoms, and secondary organ dysfunction (often renal, hepatic, or pulmonary). ARDS denotes acute respiratory distress syndrome, CRP C-reactive protein, and VEGF vascular endothelial growth factor.
Figure 2
Figure 2. Pathophysiological Features of Cytokine Storm.
Cytokine storm can occur as a result of inappropriate recognition (e.g., in hypersensitivity) or ineffective recognition with immune evasion (e.g., in Epstein–Barr virus [EBV]–associated hemophagocytic lymphohistiocytosis [HLH]), an inappropriate response with an exaggerated effector response and cytokine production (e.g., in chimeric antigen receptor [CAR] T-cell therapy) or an ineffective response due to immune evasion (e.g., in sepsis), or failure to terminate homeostasis or return to homeostasis (e.g., in HLH). Examples of drugs that can inhibit signaling pathways are shown in boxes. Covid-19 denotes coronavirus disease 2019, CS cytokine storm, IL1RA interleukin-1–receptor antagonist, IP-10 interferon-inducible protein 10, JAK-STAT3 Janus kinase–signal transducer and activator of transcription 3, MAPK mitogen-activated protein kinase, MCP-1 monocyte chemotactic protein 1, MIP-1α macrophage inflammatory protein 1α, mTOR mammalian target of rapamycin, NF-κB nuclear factor κB, TNF tumor necrosis factor, and Tregs regulatory T cells.
Figure 3
Figure 3. T-Cell Effector Subgroups Involved in Cytokine Storm.
The master transcription factors (T-bet, GATA-3, PU.1, RORγT, and eomesodermin [eomes]), effector molecules, and cell targets are shown for the following T-cell subgroups: types 1, 2, 9, and 17 helper T (Th1, Th2, Th9, and Th17, respectively) cells and cytotoxic T lymphocytes.

Comment in

  • Cytokine Storm.
    Gaestel M, Nebreda AR, Yaffe MB. Gaestel M, et al. N Engl J Med. 2021 Apr 22;384(16):e59. doi: 10.1056/NEJMc2036236. N Engl J Med. 2021. PMID: 33882214 No abstract available.
  • Cytokine Storm.
    Supady A, Bode C, Duerschmied D. Supady A, et al. N Engl J Med. 2021 Apr 22;384(16):e59. doi: 10.1056/NEJMc2036236. N Engl J Med. 2021. PMID: 33882215 No abstract available.
  • Cytokine Storm.
    Mudd PA, Crawford JC, Thomas PG. Mudd PA, et al. N Engl J Med. 2021 Apr 22;384(16):e59. doi: 10.1056/NEJMc2036236. N Engl J Med. 2021. PMID: 33882216 No abstract available.

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