What Is a Cytokine Storm?
Cytokines are a part of the immune system of the body. They are proteins produced by the cells and are vital for controlling the growth and activity of immune cells and blood cells. They mainly help in the movement of immune cells towards the target. It may act on the cells that produce them, on the nearby cells, or in some cases, distant cells. The different types of cytokines include – interferons, interleukins, chemokines, colony-stimulating factors, and tumor necrosis factors.
There is an overwhelming release of cytokines in some disease conditions, and such a condition is known as a cytokine storm. Cytokine storm is often associated with Coronavirus disease, autoinflammatory disorders, etc. It can be due to certain viral or bacterial infections, toxic shock toxins, non-infectious diseases, or even can be due to specific therapeutic interventions (cancer treatment). The cytokine storm is the main reason for death in patients affected with COVID-19. It is essential to identify cytokine storms in the initial stage itself. Otherwise, it can affect the prognosis and treatment of the underlying disease.
What Are the Features of Cytokine Storm?
Cytokine storm encompasses several disorders of immune dysregulation. It can affect the general well-being of the individual, cause systemic inflammation, and may lead to multiorgan failure. Depending upon the severity and treatment given for the underlying condition, the onset and duration of cytokine storm may vary. The main clinical features associated with cytokine storm include:
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Fatigue.
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Headache.
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Rashes.
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Joint pain.
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Muscle pain.
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Loss of appetite.
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Neuropsychiatric findings.
The above symptoms can occur due to cytokine-induced tissue damage. As the condition progresses, it can affect blood vessels and may lead to:
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Severe bleeding.
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Decreased levels of oxygen in the blood.
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Decreased blood pressure.
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Shock.
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Death.
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In some patients, respiratory symptoms like cough and rapid breathing, which may progress to acute respiratory distress syndrome (ARDS), can occur.
In cytokine storms associated with cancer treatment, it may cause neurologic toxicity and anasarca (generalized swelling of the body).
What Cytokines Are Associated With Cytokine Storm?
The major cytokines associated with cytokine storm include;
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Interferons (IFNs) – They play an important role in the body's defense system against viruses and microbial pathogens. It is of three types (I, II, and III). Due to antiviral and immunomodulatory properties, it is often used to treat hepatitis C and hepatitis B, leukemia, and multiple sclerosis.
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Interleukins – They are mainly involved in the activation of immune cells. They mainly contribute to the intercellular communication among immune cells.
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Chemokines – They are the largest group of cytokines. They mainly contribute to the migration of immune cells to the target tissue (the site of the attack by the microbes), the development and functioning of the body’s immune system, and cancer metastasis.
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Colony-Stimulating Factors – It mainly increases the number of cells that produce cytokines at the site of inflammation. It helps in perpetuating inflammatory reactions.
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Tumor Necrosis Factor (TNFs) – TNFs play a significant role in a cytokine storm. It is mainly associated with the influenza virus, dengue virus, and Ebola virus. It is often produced in excess in psoriasis, inflammatory bowel disease, and rheumatoid arthritis.
What Is the Pathology of Cytokine Storm?
Learning the pathology of cytokine storms can help understand how the condition leads to a life-threatening situation. The cytokine storm can cause inflammation at a local site, and it spreads throughout the body through blood. When the inflammation occurs in the skin or other tissue, it may cause pain or increase the temperature of that particular tissue alone. Due to these inflammatory reactions, the body initiates the compensatory repair process, and it may restore the particular tissue completely. But when the inflammatory responses are severe, it causes severe damage to local tissues, and the repair process includes fibrosis of the tissue or organ. This can lead to permanent organ damage in the case of the cytokine storm.
How to Diagnose a Cytokine Storm?
The diagnosis of cytokine storm is usually made while treating the underlying conditions. A person suffering from infectious diseases like COVID-19, autoimmune disorders like rheumatoid arthritis, or undergoing cancer treatment, can be at risk of the cytokine storm. The diagnosis includes medical history, physical examination, and laboratory investigations of the patient. If the patient is presented with fever, low oxygen in the blood, respiratory disorders, etc., along with underlying conditions mentioned above, it can be suggestive of the cytokine storm.
In the laboratory tests, an increase in C-reactive protein levels, elevated ferritin levels, elevations in serum inflammatory cytokines (interferons and interleukins) can be seen.
In the case of infectious diseases like COVID-19, a chest X-ray can give an idea about lung involvement.
How to Treat a Cytokine Storm?
The main steps in the treatment of cytokine storms are identifying the underlying condition, accessing the severity, and devising a treatment plan. The treatment plan mainly involves supportive care to maintain the organ function, control the underlying function, and avoid the trigger factors that elicit severe immune responses. The supportive treatment in severe cases may involve;
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Management of fluid and electrolyte balance.
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Monitoring of vital signs.
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Ventilatory support.
Treating the underlying conditions include intake of antibiotics or antiviral drugs depending upon the cause. Corticosteroids can be helpful if the cause is an autoimmune disease. In the cases where treating the underlying condition is not feasible, approaches to decrease the immune response can be made. Immunomodulatory drugs show a significant therapeutic benefit.
COVID-19 and Cytokine Storm:
COVID-19 is characterized by cytokine storm, life-threatening pneumonia, and multiorgan failure. In severe cases, uncontrolled levels of cytokines are realized that activate more immune cells, causing hyperinflammation. This is the main cause of severe complications associated with COVID-19.
Conclusion:
Cytokine storms occur due to severe immune dysregulation. With the advancement in the medical field, many cases of a cytokine storm are well treated. But, several researches are going on to understand the exact mechanism of cytokine storms and the conditions that have to be included in the spectrum of cytokine disorders. This can help provide better treatment to the affected individuals.
