People often get immunotherapy as a treatment for cancer. These immunotherapy treatments can be effective, but they may cause your immune system to have an unnatural response. Your body, as a result of the treatment, may produce a great amount of cytokines – proteins that affect the immune system. This could cause cytokine release syndrome (CRS).
What Is Cytokine Release Syndrome?
CRS happens when your body responds too strongly to an infection or after the use of certain immunotherapy, like CAR T-cell therapy to treat cancer. Cytokines are a type of messenger protein that help direct the body’s immune response.
In cytokine release syndrome, the number of cytokines is too high. You may have a mild reaction with a fever and flu-like symptoms. In some cases, cytokine release syndrome will cause other more serious or even life-threatening symptoms.
Cytokine release syndrome vs. cytokine storm
You might hear cytokine release syndrome called a cytokine storm. There are some similarities, but also some differences between the two conditions.
Cytokine release syndrome can happen when you have certain immunotherapies used to treat cancer. Some of those include monoclonal antibody and CAR T-cell therapies. Your immune system is triggered to produce too many cytokines.
Cytokine storm also happens when too many cytokines are released into the immune system. It’s caused by infections, autoimmune conditions, or other diseases. Some immunotherapy treatments can cause a cytokine storm. The resulting overwhelming inflammation can be very serious or life-threatening if it leads to multiple organ failure.
The effects of a cytokine storm usually come on within minutes or hours of treatment. But in cytokine release syndrome, symptoms are delayed days or weeks after treatment.
Who Does Cytokine Release Syndrome Affect?
CRS may happen if you:
Get immunotherapy for cancer. Depending on the kind of immunotherapy you have, CRS can happen within minutes or hours, or within a few days. But CRS has also shown up, in some cases, weeks after the infusion where CAR T-cell therapy is used. Children who take blinatumomab and tisagenlecleucel are at higher risk of CRS.
Have an autoimmune disease. If you have certain conditions that are passed down in families or an autoimmune disease, you may be prone to cytokine release syndrome.
Are infected with COVID-19. CRS is part of the reason some people who have COVID-19 face life-threatening complications.
Get an infection. When you have a virus or other kinds of infection, your body’s natural reaction is to trigger your immune system. If it overreacts, and releases too much cytokine, CRS happens.
Cytokine Release Syndrome Causes
Immunotherapies and infections are the main triggers of an excess of cytokines flooding your system.
Immunotherapies that are more likely to cause CRS include monoclonal antibodies and CAR T-cell therapy.
Infections like COVID-19 or influenza can cause CRS.
Cytokine Release Syndrome Symptoms
Symptoms may be mild. You might feel like you have the flu. But they can be life-threatening and affect most systems in your body.
General symptoms
- Fever
- Chills
- Headache
- Joint or muscle aches
- Skin rash
- Fatigue
- Weakness
- Loss of appetite
- Nausea
- Diarrhea
Heart symptoms
- Increased heart rate
- Low blood pressure
- Irregular heartbeat
- Decreased heart function
- Swelling
Brain and nervous system symptoms
- Confusion
- Dizziness
- Seizures
- Shaking, problems controlling movement
- Hallucinations
- Problems talking or swallowing
Lung symptoms
- Cough
- Shortness of breath
- Decreased lung function
- Reduced oxygen levels
Cytokine Release Syndrome Diagnosis
Because CRS is usually caused by an infection or immunotherapy treatment, your doctor will likely do a lot of tests to find out whether you have CRS – and how serious it is – including:
Physical exam. Your care team will take your temperature, blood pressure, heart rate, and oxygen levels. They may also test your breathing.
Medical history. Your team will want to know about the condition you’re taking immunotherapy for, as well as the type, dosage, and how often you get treatments.
Neurological exam. Medical staff will look for any changes in brain or nerve function.
Blood tests. Checking bloodwork can show how your kidneys and liver are working, and the levels of electrolytes, cytokines, and other markers for infection.
Imaging. Your doctor may order a chest X-ray, CT scan, or MRI test.
Cytokine Release Syndrome Treatments
Treatment for CRS will depend on how serious it is and what kind of symptoms you’re having. Your doctor will use a scale, 1-4, to grade your CRS. The higher the grade, the more treatment you’ll need.
To figure out the grade, the doctor will look at:
- How bad your symptoms are
- Whether you can breathe on your own
- Your heart rate and breathing rate
- Your blood pressure
- How you’re responding to treatment
- Whether your organs are damaged
Your doctor will start out by giving you medication to lower inflammation. That could include corticosteroids or medicines that target specific cytokines (such as anakinra, siltuximab, and tocilizumab).
Then, you might get other treatment, depending on your symptoms. That can include:
- IV fluids
- Medicines to control blood pressure and support heart function
- Drugs to reduce fever
- A machine to help you breathe or oxygen
- A machine to remove waste from your blood if your kidneys aren’t working well
- A blood product transfusion, a treatment that adds essential parts to your blood
- Balancing your electrolytes
Cytokine Release Syndrome Complications
It is important to pay attention to the first symptoms of CRS to avoid complications. It is best to contact your health care provider at the first sign of a fever, especially if you are getting immunotherapy as a cancer patient. If CRS is not treated, it can cause complications, including:
Drop in blood pressure. Hypotension (low blood pressure) may be a complication. You may need fluids to get your blood pressure stable.
Arrhythmias and tachycardia. An abnormal heart rhythm may result because of CRS and will likely need monitoring.
Respiratory issues. You may have shortness of breath or severe respiratory distress that may require oxygen.
Multi-system organ failure. Several organs, like your heart, kidneys, and liver, may fail. Intensive support will be required if this happens.
Blood disorder issues. Bleeding or clotting disorders are possible, particularly if your CRS is caused by COVID-19.
Cardiovascular complications. You may have damage to your heart as a result of the inflammation.
How Can You Prevent Cytokine Release Syndrome?
There is no proven way to completely stop CRS from happening. Managing CRS requires a balancing act of protecting the effectiveness of immunotherapies while making CRS less serious. Your doctor may do that by:
Reducing CAR T cells. Lowering disease burden via debulking chemotherapy before CAR T-cell therapy or reducing CAR T-cell dose may make CRS less frequent and less severe.
Pausing bispecific T-cell engager therapy. This immunotherapy that targets tumor cells can be adjusted or paused in response to toxicity.
CRS Takeaways
Cytokine release syndrome is caused by the release of too many cytokines from immune cells usually in people getting immunotherapy for cancer treatment (such as CAR T). It may also affect people who have autoimmune disease and/or severe infections (including COVID).
CRS symptoms include a fever, nausea, headaches, rashes, and shortness of breath, and they can range from mild to serious.
People who are having immunotherapy should watch for symptoms, most commonly a fever. Your doctor will first try to bring down your inflammation. Treatment options for CRS depend on your symptoms and how serious they are.
Cytokine Release Syndrome FAQs
How long does cytokine release syndrome last?
It depends on how serious your illness is. If you get cytokine release syndrome because of immunotherapy treatments, you may recover in one or two weeks.
What triggers cytokine release?
Infections and immunotherapies are the main triggers of the release of too many cytokines. Cytokines are usually helpful, and the release of them is a normal response to infections. But too many cytokines in your system can cause a mild to life-threatening reaction, depending on several things.
What does a cytokine storm feel like?
During a cytokine storm, you will likely have a high fever, feel inflamed (which will cause redness and swelling), and have nausea and severe tiredness. In some cases, a cytokine storm may be severe and life-threatening and could lead to organ failure.
