Table of ContentsView AllTable of ContentsWhat It IsGradesSymptomsCausesDiagnosisTreatmentCytokines and COVID-19PreventionSeeking Medical Care
Table of ContentsView All
View All
Table of Contents
What It Is
Grades
Symptoms
Causes
Diagnosis
Treatment
Cytokines and COVID-19
Prevention
Seeking Medical Care
Formerly used interchangeably with the term “cytokine storm,” CRS is a systemic inflammatory response syndrome (SIRS), an inflammatory condition that impacts all of the body’s systems.Typical symptoms include fever, a racing heart, low blood pressure, shortness of breath, and skin rash. In some cases, cytokine release syndrome can be severe or even fatal.
This article covers everything you need to know about cytokine release syndrome, including symptoms, treatment options, and prevention.
Boyloso / Getty Images
What Is a Cytokine?
Cytokines are tiny proteins that play an important role in the body’s immune response. They “tell” the immune system how to fight off pathogens and illnesses, such as viruses and cancer.
Examples includeinterleukins, which behave as messengers between illness-fightingwhite blood cells, andinterferons, which help to improve the body’s ability to combat cancer cells. Some laboratory-made cytokines are used to treat cancer and other serious conditions.
A Word From VerywellSymptoms can range from mild flu-like symptoms to severe life-threatening symptoms. Cytokine release syndrome is treatable. Consult your healthcare provider right away if you have risk factors and are developing symptoms suggesting CRS after COVID-19 infection, receiving an infusion or injection of antibody immunotherapy.—JURAIRAT J. MOLINA, MD, MEDICAL EXPERT BOARD
A Word From Verywell
Symptoms can range from mild flu-like symptoms to severe life-threatening symptoms. Cytokine release syndrome is treatable. Consult your healthcare provider right away if you have risk factors and are developing symptoms suggesting CRS after COVID-19 infection, receiving an infusion or injection of antibody immunotherapy.—JURAIRAT J. MOLINA, MD, MEDICAL EXPERT BOARD
Symptoms can range from mild flu-like symptoms to severe life-threatening symptoms. Cytokine release syndrome is treatable. Consult your healthcare provider right away if you have risk factors and are developing symptoms suggesting CRS after COVID-19 infection, receiving an infusion or injection of antibody immunotherapy.
—JURAIRAT J. MOLINA, MD, MEDICAL EXPERT BOARD
Are There Different Stages of Cytokine Release Syndrome?
Established in 2014, the Revised Cardiac Risk Index, or the Lee criteria, assesses cardiac risk and includes the following five grades of cytokine release syndrome:
Cytokine Release Syndrome Symptoms
Cytokine release syndrome can affect the entire body. The most common symptoms of cytokine release syndrome include:
Heart and Blood Vessels
As it progresses, cytokine release syndrome may start to affect the cardiovascular and circulatory systems, meaning it impacts the heart and blood vessels. Symptoms may range from mild to serious or even life-threatening. They may include:
Brain and Nervous System
In particular, cancer-fighting chimeric antigen receptor (CAR)T-celltherapies, which work to prevent infection and fight existing conditions, often lead to cytokine release syndrome with neurotoxicity. These are problems within the nervous system. Some possible neurological symptoms are:
Lungs
Many people have respiratory symptoms as a result of cytokine release syndrome, such as:
What Causes Cytokine Release Syndrome?
Common triggers for cytokine release syndrome are:
How Is Cytokine Release Syndrome Diagnosed?
In addition to elevated levels of certain cytokines in your blood, some of the biomarkers of cytokine release syndrome that your healthcare provider may test for include:
Cytokine release syndrome can be confused with several other conditions, such as:
Part of the diagnostic process for cytokine release syndrome involves ensuring the above conditions are not causing symptoms.
Cytokine Release Syndrome Requires Prompt Treatment
Cytokine release syndrome is treatable, but it needs to be addressed right away to prevent serious complications. Mild to moderate CRS can be treated primarily with supportive care to manage symptoms, such as intravenous (IV) fluids,antihistamines, antipyretics to reduce fever, or vasopressors to regulate blood pressure.
Low-flow oxygen therapy may be helpful in relieving mild respiratory symptoms. People who have trouble breathing on their own may require more intensive interventions, such as mechanical ventilation or a continuous positive airway pressure (CPAP) machine.
Actemra(tocilizumab), which works to suppress the immune system and reduce inflammation, has been found to help treat severe cytokine release syndrome in children over 2 years old and adult patients. Other medications that work similarly include:
Pro-inflammatory cytokines have been found to play a major role in the severity and duration of COVID-19. People who get CRS after developing COVID-19 tend to have a harder time with recovery from the virus, as well as more complications along the way.
People with other inflammatory disorders, such asrheumatoid arthritis(RA), and people who are immunocompromised due to health conditions or treatments are significantly more likely to experience cytokine release syndrome alongside COVID-19.
How to Prevent Cytokine Release Syndrome
There are several risk factors that may increase your risk of developing cytokine release syndrome after receiving immunotherapy or getting an infection, such as:
You are also more likely to develop a severe case of CRS if your symptoms begin within 72 hours or less of receiving treatment.
Both JAK/STAT (Janus kinase/signal transducer and activator of transcription protein) inhibitors, such asJakafi(ruxolitinib), and LENZ (lenzilumab), a monoclonal antibody, are effective in preventing CRS among people receiving CAR T-cell therapy.
Some research also suggests prophylactic (preventive) treatment with Blincyto orsystemic corticosteroidsas a means of prevention.
When to Contact a Healthcare Provider
Getting early treatment is especially important in order to prevent existing cases of CRS from getting worse and becoming life-threatening. If you are going to undergo immunotherapy, discuss your concerns about CRS. Let your healthcare provider know about any other medications you’re taking, as well as your medical history.
If you’ve recently developed an infection or undergone a treatment that could cause CRS and develop potential symptoms, such as fatigue, fever, or shortness of breath, tell your healthcare provider right away.
Summary
Cytokine release syndrome occurs when a flood of cytokines is set loose into the body all at once, leading to a systemic inflammatory reaction. This often happens as a result of immunotherapy, although it can also occur due to infection. Many people with CRS only have mild to moderate flu-like symptoms, but others develop life-threatening complications such as kidney orliver failure.
If you suspect that you may have a high risk of developing CRS, talk to your healthcare provider right away about the best course of action. Early diagnosis and management of symptoms is key in preventing serious complications and reducing the severity and duration of the illness.
9 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.National Cancer Institute.Cytokine release syndrome.Shimabukuro-Vornhagen A, Gödel P, Subklewe M, et al.Cytokine release syndrome.J Immunother Cancer. 2018;6(1):56. doi:10.1186/s40425-018-0343-9American Cancer Society.Cytokines and their side effects.Tvedt THA, Vo AK, Bruserud Ø, Reikvam H.Cytokine release syndrome in the immunotherapy of hematological malignancies: The biology behind and possible clinical consequences.J Clin Med. 2021;10(21):5190. doi:10.3390/jcm10215190National Cancer Institute.T cell.MedlinePlus.Talquetamab-tgvs.Murthy H, Iqbal M, Chavez JC, Kharfan-Dabaja MA.Cytokine release syndrome: Current perspectives.Immunotargets Ther. doi: 10.2147/ITT.S202015Murthy H, Iqbal M, Chavez JC, Kharfan-Dabaja MA.Cytokine release syndrome: Current perspectives.Immunotargets Ther. 2019;8:43-52. doi:10.2147/ITT.S202015Tanveer A, Akhtar B, Sharif A, et al.Pathogenic role of cytokines in COVID-19, its association with contributing co-morbidities and possible therapeutic regimens.Inflammopharmacology. 2022;30(5):1503-1516. doi:10.1007/s10787-022-01040-9
9 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.National Cancer Institute.Cytokine release syndrome.Shimabukuro-Vornhagen A, Gödel P, Subklewe M, et al.Cytokine release syndrome.J Immunother Cancer. 2018;6(1):56. doi:10.1186/s40425-018-0343-9American Cancer Society.Cytokines and their side effects.Tvedt THA, Vo AK, Bruserud Ø, Reikvam H.Cytokine release syndrome in the immunotherapy of hematological malignancies: The biology behind and possible clinical consequences.J Clin Med. 2021;10(21):5190. doi:10.3390/jcm10215190National Cancer Institute.T cell.MedlinePlus.Talquetamab-tgvs.Murthy H, Iqbal M, Chavez JC, Kharfan-Dabaja MA.Cytokine release syndrome: Current perspectives.Immunotargets Ther. doi: 10.2147/ITT.S202015Murthy H, Iqbal M, Chavez JC, Kharfan-Dabaja MA.Cytokine release syndrome: Current perspectives.Immunotargets Ther. 2019;8:43-52. doi:10.2147/ITT.S202015Tanveer A, Akhtar B, Sharif A, et al.Pathogenic role of cytokines in COVID-19, its association with contributing co-morbidities and possible therapeutic regimens.Inflammopharmacology. 2022;30(5):1503-1516. doi:10.1007/s10787-022-01040-9
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
National Cancer Institute.Cytokine release syndrome.Shimabukuro-Vornhagen A, Gödel P, Subklewe M, et al.Cytokine release syndrome.J Immunother Cancer. 2018;6(1):56. doi:10.1186/s40425-018-0343-9American Cancer Society.Cytokines and their side effects.Tvedt THA, Vo AK, Bruserud Ø, Reikvam H.Cytokine release syndrome in the immunotherapy of hematological malignancies: The biology behind and possible clinical consequences.J Clin Med. 2021;10(21):5190. doi:10.3390/jcm10215190National Cancer Institute.T cell.MedlinePlus.Talquetamab-tgvs.Murthy H, Iqbal M, Chavez JC, Kharfan-Dabaja MA.Cytokine release syndrome: Current perspectives.Immunotargets Ther. doi: 10.2147/ITT.S202015Murthy H, Iqbal M, Chavez JC, Kharfan-Dabaja MA.Cytokine release syndrome: Current perspectives.Immunotargets Ther. 2019;8:43-52. doi:10.2147/ITT.S202015Tanveer A, Akhtar B, Sharif A, et al.Pathogenic role of cytokines in COVID-19, its association with contributing co-morbidities and possible therapeutic regimens.Inflammopharmacology. 2022;30(5):1503-1516. doi:10.1007/s10787-022-01040-9
National Cancer Institute.Cytokine release syndrome.
Shimabukuro-Vornhagen A, Gödel P, Subklewe M, et al.Cytokine release syndrome.J Immunother Cancer. 2018;6(1):56. doi:10.1186/s40425-018-0343-9
American Cancer Society.Cytokines and their side effects.
Tvedt THA, Vo AK, Bruserud Ø, Reikvam H.Cytokine release syndrome in the immunotherapy of hematological malignancies: The biology behind and possible clinical consequences.J Clin Med. 2021;10(21):5190. doi:10.3390/jcm10215190
National Cancer Institute.T cell.
MedlinePlus.Talquetamab-tgvs.
Murthy H, Iqbal M, Chavez JC, Kharfan-Dabaja MA.Cytokine release syndrome: Current perspectives.Immunotargets Ther. doi: 10.2147/ITT.S202015
Murthy H, Iqbal M, Chavez JC, Kharfan-Dabaja MA.Cytokine release syndrome: Current perspectives.Immunotargets Ther. 2019;8:43-52. doi:10.2147/ITT.S202015
Tanveer A, Akhtar B, Sharif A, et al.Pathogenic role of cytokines in COVID-19, its association with contributing co-morbidities and possible therapeutic regimens.Inflammopharmacology. 2022;30(5):1503-1516. doi:10.1007/s10787-022-01040-9
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