With the arrival of the novel coronavirus that causes COVID-19, we are all learning a new medical vocabulary – some of it so complex a doctor needs to explain it. One of these terms is “cytokine storm,” which describes an event that takes place in the immune system in response to various circumstances, including infections like COVID-19.

What are cytokines?

Cytokines are a class of signaling proteins. These proteins are released from many types of cells to initiate or regulate a whole range of functions, such as inflammation, growth, tissue repair, and many aspects of immune function.

What do cytokines normally do in the body?

Although cytokines regulate literally hundreds of bodily processes, in the immune system they are critically important for regulating inflammation and orchestrating how the body responds to a viral infection.1 Under normal circumstances, when you are exposed to a viral infection, as the virus gets into your cells it causes the infected cells to release cytokines called early inflammatory mediators – these cytokines call your immune cells to action.

These “first responder” immune cells – macrophages and natural killer cells – release their own cytokines that direct the immune system to combat the infection, ultimately calling on cells that make antibodies (B cells) so your body can do a more efficient job fighting the infection in the future.

Along the way, some of these cytokines can make you uncomfortable – they raise your body temperature, they cause inflammation that makes you ache, they encourage mucous production, and more – but all with the end goal of protecting you and getting you back to being your healthy self.

After they have done their job, cytokines are broken down very rapidly – which is important. If they stayed around too long (and sometimes they do), they can quickly go from being helpful to harmful. 

What is a cytokine storm?

In a sense, a cytokine storm is way too much of a good thing. In a cytokine storm, the immune system goes from a tightly coordinated response to a state of hyperactive overdrive.

Cytokine production goes unchecked, with immune cells and immune activity rapidly spreading throughout the body – even to the point of attacking healthy organs and tissues. Inflammation also spirals out of control. This over-reaction leads to high fever, low (sometimes dangerously) blood pressure, and potentially widespread damage to the lungs, kidneys, and blood vessels.

This reaction is very serious and can even be fatal. Even in individuals who recover, the massive inflammation can lead to long-term organ damage due to scarring and fibrosis.

Although currently associated with COVID-19, cytokine storms can occur in a whole range of other conditions,2 such as influenza, cytomegalovirus, Epstein-Barr virus, Streptococcus (“strep”), multiple sclerosis, pancreatitis, some cancers, and graft-host disease. A treatment used for some cancers, called chimeric antigen receptor T-cell therapy (CAR T-cell), can also trigger a cytokine storm.3

Are some individuals more susceptible?

Because we know that humans aren’t all the same, it is reasonable to ask, “Who does this happen to?” Researchers have started to identify certain genetic markers4 that might make some individuals more susceptible to a cytokine storm than others, but it will probably be some time before there is a test to determine this.

Other pre-existing conditions, such as obesity5 and diabetes, can also predispose a person to developing a cytokine storm, which could account for higher rates of hospitalization and death in these individuals.

How can a cytokine storm be stopped?

Physicians generally use anti-inflammatory medications that “dampen” the immune system to control a cytokine storm. Examples are corticosteroids or TNF-alpha blockers.

Medications can also be prescribed that support the specific organs being impacted or that raise blood pressure or lower fever. There are some nutrients – especially those that target free radicals – that have shown early promise in animal studies in helping to stop a cytokine storm, but it is important to know that this data is very early, and not yet known to have similar effects in humans.

Compounds being studied include astaxanthin, curcumin, licorice, vitamin C, and vitamin E. Of course, the most important measure is to identify this complication quickly to ensure a patient is treated for it.

References

  1. Zdravkovic N, Rosic M, Lutovac M, Zdravkovic V. Physiology and pathology of cytokine: commercial production and medical use. Physiol Pathol Immunol December 2017. doi:10.5772/intechopen.72200
  2. Tisoncik J, Korth M, Simmons C, et al. Into the eye of the cytokine storm. Microbiol Mol Biol Rev MMBR 2012;76(1):16-32. doi:10.1128/MMBR.05015-11
  3. Giavridis T, van der Stegen S, Eyquem J, et al. CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nat Med 2018;24(6):731-738. doi:10.1038/s41591-018-0041-7
  4. Windsor M. Here’s a playbook for stopping deadly cytokine storm syndrome – The Reporter. https://www.uab.edu/reporter/know-more/publications/item/8909-here-s-a-playbook-for-stopping-deadly-cytokine-storm-syndrome. [Accessed April 29, 2020.]
  5. Ramos-Muniz M, Palfreeman M, Setzu N, et al. Obesity exacerbates the cytokine storm elicited by Francisella tularensis infection of females and is associated with increased mortality. Biomed Res Int 2018 Jun 26;2018:3412732. doi: 10.1155/2018/3412732.