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Cytokine storm.

Rajendra Karki1,2,3, Mihai G Netea4,5, Caroline Diorio6,7

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|January 15, 2026
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Cytokine storm, an overactivated immune response, causes dangerous inflammation and organ damage. Understanding its positive feedback loop involving cytokines and cell death is key to developing new treatments.

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Area of Science:

  • Immunology
  • Cell Biology
  • Pathophysiology

Background:

  • Cytokine storm involves elevated circulating cytokines from overactivated immune responses, leading to tissue damage and potential lethality.
  • It can be triggered by infections, autoimmune diseases, genetic factors, or medical treatments, complicating diagnosis and management.
  • Conserved molecular mechanisms underlying cytokine storm offer potential therapeutic targets.

Purpose of the Study:

  • To elucidate the molecular and cellular mechanisms driving cytokine storm.
  • To identify conserved pathways that can inform therapeutic strategies for cytokine storm.

Main Methods:

  • Review of existing studies on cytokine storm.
  • Analysis of molecular signaling pathways.
  • Investigation of inflammatory cell death mechanisms, including PANoptosis.

Main Results:

  • Cytokine storm is initiated by cytokine production and amplified by a positive feedback loop between cytokines and inflammatory cell death (PANoptosis).
  • Cells release cytokines through canonical secretion or lytic cell death (pyroptosis, PANoptosis).
  • Released cytokines and damage-associated molecules induce paracrine PANoptosis in neighboring cells, further amplifying the cycle.

Conclusions:

  • Understanding the positive feedback loop between cytokines and PANoptosis is crucial for comprehending cytokine storm.
  • Targeting these conserved molecular mechanisms is essential for developing effective therapies to improve patient outcomes.