Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Dec 3;383(23):2255-2273.
doi: 10.1056/NEJMra2026131.

Cytokine Storm

David C Fajgenbaum  1 , Carl H June  1
Affiliations
Review

Cytokine Storm

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

PubMed Disclaimer

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.
See this image and copyright information in PMC

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.

References

    1. Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 2010;18:843-851. - PMC - PubMed
    1. Ferrara JL, Abhyankar S, Gilliland DG. Cytokine storm of graft-versus-host disease: a critical effector role for interleukin-1. Transplant Proc 1993;25:1216-1217. - PubMed
    1. Chatenoud L, Ferran C, Bach JF. The anti-CD3-induced syndrome: a consequence of massive in vivo cell activation. Curr Top Microbiol Immunol 1991;174:121-134. - PubMed
    1. Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas: with a report of ten original cases. Am J Med Sci 1893;105:487-511. - PubMed
    1. Pechous RD, Sivaraman V, Price PA, Stasulli NM, Goldman WE. Early host cell targets of Yersinia pestis during primary pneumonic plague. PLoS Pathog 2013;9(10):e1003679-e1003679. - PMC - PubMed

MeSH terms