Last updated on May 7, 2020
Last week, I very briefly brought up the concept of a “cytokine storm,” a dangerous immune response to a perceived threat. Cytokine storms have been linked to Covid-19 related deaths—where, in some cases, patients weather the disease itself for some time only to suddenly crash. Cytokines could even possibly be the culprit behind the blood clots and strokes that are being seen in some Covid-19 patients (although this has not been confirmed—the prevalence of blood clots in Covid-19 patients may be a direct consequence of the virus).
Cytokine storms are immune system overreactions that can happen towards the end of an infection or even after the infection has abated. On the precipice of victory, the immune system decides to carpet bomb their own territorycausing far more damage than the virus did in the first place. Scientists don’t know why certain patients develop cytokine storms in response to Covid-19 when others don’t. It may be genetic, it may be loosely related to age, or it may be just random.
But what is a cytokine, and why does the immune system release so many of them in response to a perceived threat? There are a variety of types of cytokines, but all of them are small proteins released from immune cells that can bind to receptors and modulate immune responses. The proteins are short-lived, but they can bind to the cell that made them to promote more cytokine production. They also bind to nearby cells and travel through the blood stream to modulate distant cells. One of the main manufacturers of cytokines are helper T-cells, specialized immune cells that direct the immune response to a pathogen by releasing cytokines, promoting B-cell antibody production, and activating immune cells.
Cytokines are essentially signaling molecules that coordinate the body’s immune response to an invasion. They can promote inflammation, repress inflammation, inhibit viral replication within cells, attract other immune factors to an inflammation site, activate cell proliferation, or order cells to destroy themselves for the good of your body (like spies, cells carry “cyanide pills” that they can activate when signaled resulting in cell death—this occurs to stop infections and also as a part of normal tissue development).
The cytokine system is extremely efficient at creating a coordinated immune response to any perceived threat. A single cytokine can regulate multiple immune responses (an attribute known as pleiotropy). Different cytokines regulate the same immune responses (redundancy—important in case one type of cytokine is knocked out). Cytokines can have synergistic properties, meaning that multiple cytokines can create a bigger immune response than their additive effect alone would produce (the mechanism that creates cytokine storms). Some cytokines can offset or inhibit the effect of other cytokines (antagonism).
Sometimes, cytokines, like a dog trying to attack the mailman, can create an extreme immune response to a perceived threat that isn’t a really threat at all. This is the case in organ transplants and other therapies that introduce foreign objects into the body. Often times, doctors have to modulate the immune response to these potentially life-saving therapies by suppressing the patient’s immune system or removing cytokines from the blood via dialysis.
Cytokines are necessary to mount a proper immune response to an infection. This is why doctors may give cytokines to patients with compromised immune systems. Cytokines can also be used to enhance the efficacy of vaccines and cancer therapies.
Cytokines clearly play an important role in coordinating the immune system’s defensive and offensive strategies against pathogen invasion. But then why do they cause some patients to have severe reactions that sometimes result in death? In a cytokine storm (also known as cytokine release syndrome), immune cells pump out lots of cytokines in response to a pathogen, like Covid-19. As the number of cytokines in the blood stream increases, they stimulate the development of more immune cells, recruit immune cells to inflammation sites, and trigger more cytokine release. This positive feedback loop may be successful at driving out the enemy invader, but it can also be damaging to native body cells if it continues on too long. Inflammation causes high fever, swelling, pain, and eventually tissue damage. In the case of Covid-19, where most of the immune cells are recruited to the lungs, inflammation can lead to a buildup of fluid that can prevent oxygen from getting into the blood.
Scientists aren’t completely sure why some people suffer from cytokine storms more than others. Age seems to play a factor, but cytokine storms are also killing a subset of young, healthy people who contract the illness (even leaving out those that suffer from blood clots). There is also the question of why certain diseases, like Covid-19, seem more likely to trigger a cytokine storm. Doctors have been struggling to treat patients suffering from cytokine storms without leaving them completely defenseless to the disease. Treatments to modulate cytokine levels have been used when possible. Steroids, which suppress the immune system, are more likely to be used—despite their dangerous side effects—since they are more readily available. But researchers are looking for better methods, since getting control of cytokine storms may be our best bet for reducing Covid-19 deaths.Comment below or email me at contact@anyonecanscience.com to let me know what you think about this week’s blog post and tell me what sorts of topics you want me to cover in the future. And subscribe below for weekly science posts sent straight to your email!
