Cytokine Storm: When the Immune System Attacks the Body

Cytokine Storm: When the Immune System Attacks the Body

What happens when your protector turns into an aggressive and violent attacker?

For many critical COVID-19 patients, this very betrayal (of sorts) is the cause for fatal complications and death. When the immune system, which should ideally be targeting antigens that enter the body, turns against the healthy tissues and starts attacking them as well, the results are, more often than not, lethal. This overreaction of the immune system is known as a ‘cytokine storm’, causing blockages and organ failures. What exactly happens and how does it factor into cases of the novel coronavirus?

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Understanding the Cytokine Storm: What Goes so Wrong?

In conversation with FIT, Dr Susheel Bindroo, head, Interventional Pulmonology at Jaslok Hospital, explained, “There are two types of immunity in the body: innate and adaptive. You are born with the former, and the latter develops when a person is exposed to a microbe.”

Dr Susheel Bindroo“When a pathogen enters the body, the innate immunity tries to contain it. But it is weak, and most of the pathogens can breach it. This is where adaptive immunity gets activated by recognising the antigens and working against them.”

Cytokines are proteins released by a broad range of cells in the body to trigger an immune response against an antigen, by coordinating the action at the region of infection, directing immune cells to the site, and eventually causing inflammation. This is the body’s natural defense mechanism and is an important part of the healing process.

Sometimes, however, this immune response goes into overdrive by an excessive and exorbitant amount of cytokine production, turning the ‘localised’ inflammation into hyper-inflammation, impacting not just the infected areas, but the rest of the body as well. This unregulated and uncontrolled production of cytokines is known as a ‘cytokine storm’ - as the name suggests.

Dr Susheel Bindroo“The production of cytokines is actually a protective mechanism to contain the spread of a pathogen and stop the exposure. But when the balance between pro-inflammatory and anti-inflammatory mediators in the body is hampered, leaning heavily towards the pro-inflammatory response, it starts targeting the body’s own healthy tissues along with the pathogen. This is essentially what characterises a cytokine storm.”

What Makes This Overproduction of Immune Cells & Cytokines Fatal?

There are multiple ways in which the hyper-inflammation leads to severe complications and death. Dr Bindroo explains that the this can cause Disseminated Intravascular Coagulation (DIC), which means the formation of blood clots or clumps in the blood vessels, and the inhibition of the blood flow to the different organs, causing multiple organ failure.

Dr Susheel Bindroo“When four or more organs in the body fail because of this, the mortality rate is usually above 90 percent. This is what happens in many critical patients of COVID-19.”

The observation of cytokine storms in severe cases of the novel coronavirus first came up in a study of 29 patients in Wuhan, when doctors reported high levels of cytokines IL-2R and IL-6 in their bodies. This was also seen in another research conducted on 11 patients in a Chinese province, and in a 150-patient analysis in Wuhan which found that molecular indicators for a cytokine storm were higher in those who died than in the survivors.

But cytokine storms are not exclusive to COVID-19. They have been observed in flu and other respiratory diseases caused by coronaviruses such as SARS and MERS, others such as multiple sclerosis and pancreatitis, and autoimmune diseases and conditions, the United States National Cancer Institute (NCI) has stated.

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How Do Doctors Diagnose and Treat It?

While such a response is seen in other diseases, Dr Bindroo shares that a possible difference with COVID-19 is that the incidence of DIC appears to be higher in these patients, and if that is developed, the chances of death increase significantly.

“To know whether a patient’s body is under a cytokine storm, we are measuring Interleukin-6 (IL-6) levels (this is a pro-inflammatory cytokine). If these are alleviated, we give anti-IL-6 antibodies in two spaced-out doses; the second one only if the first one shows positive effects,” he says.

Moreover, the treatment has to work in a way that the complete immune response and the mediators are not halted altogether, because we need them to fight the virus and other pathogens.

Another method being explored, which is more specific to the specific coronavirus, is plasma therapy, where the plasma from recovered patients is given to patients with severe infection. None of these has been approved yet, but the IL-6 is what doctors are following more commonly for now, he explains.

Trials are underway to test antibodies that clog the IL-6 receptor, especially for drugs that have been approved for autoimmune conditions such as rheumatoid arthritis, in cancer patients receiving immunotherapy, and for those who are genetically predisposed for a cytokine storm. A similar logic also underpins experiments on a sepsis drug - known to be effective in blocking molecules causing inflammation - to be repurposed for COVID-19, as FIT had reported earlier.

What’s most important, right now, is to recognise when the body enters this overdrive, so that it can be stopped on time.

Dr Susheel Bindroo“People on ventilators tend to have this, so we are constantly measuring the IL-6 levels in them, and mostly finding them to be high in these critical cases.”

“It’s important to keep in mind, that even in COVID-19 infections, only 10-20% will be severe cases, and from them, merely 10-15% will experience this immune overreaction and inflammation.” Dr Bindroo says.

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