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12 Jun 2021

What is Cytokine Storm?

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Cytokine Storm is a severe immune reaction in which the body releases too many cytokines into the blood too quickly. Cytokines play an important role in normal immune responses, but having a large amount of them released in the body all at once can be harmful. A cytokine storm can occur as a result of an infection, autoimmune condition, or other disease. It may also occur after treatment with some types of immunotherapy. Signs and symptoms include high fever, inflammation (redness and swelling), and severe fatigue and nausea. Sometimes, a cytokine storm may be severe or life threatening and lead to multiple organ failure. Also called hypercytokinemia.

What are cytokines?

Cytokines are small glycoproteins produced by various types of cells throughout the body. Upon their release, cytokines can promote a wide range of functions, some of which involve the control of cell proliferation and differentiation processes, autocrine, paracrine and/or endocrine activity, as well as regulating immune and inflammatory responses.

Some of the most widely studied cytokines include interferons (IFNs), interleukins, chemokines, colony-stimulating factors (CSFs), and tumor necrosis factor (TNF). The specific actions of each of these important cytokines are detailed in Table 1.

Cytokine

Actions

Types

Interferons

  • Regulate innate immunity to viruses and other pathogens
  • Antiproliferative effects
  • Type I (IFN-a and IFN-b)
  • Type 2 (IFN-g)

Interleukins

  • Regulate immune cell differentiation and activation
  • Can have pro- or anti-inflammatory effects
  • IL-1

 

Chemokines

  • The largest family of cytokines
  • Chemoattractants
  • Control the migration of immune cells
  • Contribute to embryogenesis, the development of the innate and adaptive immune systems and cancer metastasis
  • CXC
  • CC
  • C
  • CX3C

Colony-stimulating factors (CSFs)

  • Associated with inflammation
  • Participate in amplification cascade that can promote inflammatory responses
  • Granulocyte CSF (G-CSF)
  • Macrophage CSF (M-CSF)
  • Granulocyte-macrophage CSF (GM-CSF)

Tumor necrosis factor (TNF)

  • Plays an important role in the cytokine storm
  • Excessive production can lead to chronic inflammatory and autoimmune diseases
  • TNF-a

In addition to this normal response to inflammation, a cytokine storm can also occur. During a cytokine storm, various inflammatory cytokines are produced at a much higher rate than normal. This overproduction of cytokines causes positive feedback on other immune cells to occur, which allows for more immune cells to be recruited to the site of injury that can lead to organ damage.

One of the most notable clinical conditions that are associated with cytokine storms includes acute respiratory distress syndrome (ARDS), which has accounted for a significant number of deaths from SARS-CoV-2.

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