Why Does Cytokine Storm Occur?

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The human body has an innate self-regulate system that makes up a fully functional biological machinery. Whenever some pathogen enters the body, the immune system kicks into high gear mitigating the damage or, in extreme cases, eliminating the offending material completely. 

Inflammatory mediators are released as part of the immune response. One of the primary groups of inflammatory mediators is Cytokines, including pro-inflammatory cytokines and anti-inflammatory cytokines. Such as:

  • Interleukins 
  • Tumor necrosis factor (TNF), 
  • Granulocyte colony-stimulating factor (G-CSF), 
  • Monocyte chemoattractant protein-1 
  • C-reactive protein
  • Ferritin

Here you can learn how cytokines typically function and where things go wrong, potentially leading to unsettling effects. 

A Brief History of Cytokines and Immune Response:

In case of infection, your body activates a series of immune responses to send various cells. Such as:

  • Macrophages: 

These cells attack and engulf the harmful material. 

  • White blood cells, including B-cells and T-cells: 

Antibodies are made by B-cells, which then bind to pathogens and mark them as dangerous. T-cells eliminate those marked pathogens.

  • Cytokines:
    These inflammatory mediators convey the entire process, instructing the body to produce more immune cells. Thus, cytokines coordinate an all-out assault on the pathogens.

That’s how cytokines typically proceed in a healthy immune response. Let’s look into where things go wrong.

The Cytokine Storm:

Excessive or uncontrolled production and release of pro-inflammatory cytokines are called a “Cytokine Storm, Cytokine Release Syndrome (CRS), or Cytokine-associated Toxicity.” It is associated with a wide range of disorders, both infectious and non-infectious.

What Causes the Cytokine Storm?

Although the exact etiology of cytokine storm is unclear, it may result from an aggressive reaction by the immune system when confronted with an unknown, highly pathogenic invader.

Some immune therapies, such as CAR T-Cell Therapy which treats certain blood cancers, may also initiate cytokine storms.

Cytokine storms pose a severe threat to organs and tissues. A cytokine storm, for instance, can cause fluids and immune cells like macrophages to accumulate in the lungs and eventually block the airways, leading to asphyxia (suffocation) and death.

Another possible risk of cytokine storm can be extremely low blood pressure that leads to increased blood clotting, which might jeopardize normal heart function. Consequently, leading to organ dysfunction and death.  

Early Symptoms of the Cytokine Storm:

It can be challenging to diagnose the symptoms of different cytokine storms (CSS) that might manifest similarly. Cytokines cause flu-related fever, inflammation, runny nose, and muscle and joint pains.

The severity of these symptoms varies; at times, they may be tolerable, and at certain times they could be fatal. Additional symptoms may include:

  • Shortness of breath or rapid breathing 
  • Fatigue and poor responsiveness
  • Confusion and hallucinations
  • Swelling of hands and feet
  • Nausea and vomiting
  • Seizures and tremor
  • Rash

Cytokine Storm Sweating: 

In lab testing, the cytokines are always trending high in patients. The pro-inflammatory cytokines are:

  • Tumor necrosis factor-alpha
  • Interleukin-1
  • Interleukin-6

The anti-inflammatory cytokines are:

  • Interleukin 10 
  • Interleukin 1 receptor antagonist

The cytokine storm is difficult to cure, but sweat sensors can help doctors catch it early. Prompt therapy is key to averting organ failure and mortality caused by a cytokine storm.

Cytokine Storm Treatment: 

There are several different classes of medications used to treat cytokine storm, including but not limited to:

  • OX40 IG 
  • ACE inhibitors
  • Angiotensin II Receptor Blockers
  • Corticosteroids
  • Gemfibrozil
  • Free radical scavengers
  • TNF-alpha blockers

Natural Management of Cytokine Storm:

Immunosuppressants derived from plants may be the best option to combat the cytokine storm directly at the site of infection. The following are examples of plant-based agents that act as suppressants:

  • Curcumin: a primary polyphenol derived from the spice turmeric 
  • Luteolin: a flavone found in several vegetables as an antioxidant
  • Resveratrol: a phenol found in several fruits 
  • Piperine: an alkaloid found in black peppers

These ingredients prevent the production and release of pro-inflammatory cytokines.

Cytokine Storm and COVID-19:

According to observational studies, the severity of COVID-19 correlates with higher cytokine concentrations.


Who are at higher risk of developing severe illness from COVID-19?

People over the age of 65 make up the bulk of the COVID-19 susceptible population because of their weakened immune systems. COVID-19 is also more likely to spread among those who already have weakened immune systems due to preexisting chronic disorders like asthma, diabetes, or cancer.

What are some symptoms of long COVID-19 syndrome?

The general symptoms include:

  • Fatigue
  • Fever 

Respiratory symptoms include:

  • Breathing difficulty
  • Shortness of breath
  • Cough 

Neurological symptoms include:

  • Lack of concentration  
  • Headache and sleep problems
  • The feeling of pinching and distress
  • Lack of taste or smell

How long do COVID-19 symptoms usually last?

Some people might get better in a week or two. Depending on the person and the intensity of the infection, the symptoms could last up to a month. However, for some, the process could take up to a year, with or without organ malfunction.

Can COVID-19 spread through the water while swimming?

No evidence is available about the spread of COVID-19 through the water while swimming.

Are smokers more likely to develop severe diseases with COVID-19?

Due to decreased levels of interferon beta, an antiviral molecule, smoking increases the likelihood of getting COVID-19 disease and may even enhance the risk of death from the infection.

Author: Samsa Latif

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