Cytokine Release Syndrome

Author: Courtney Misher, MPH, BS R.T.(T)
Last Reviewed: March 17, 2023

What is a cytokine?

A cytokine is a small protein that lets your body know when an immune response is needed. They play an important part in communication between cells when your body may be stressed due to inflammation, infection, or trauma.

What is cytokine release syndrome?

Cytokine release syndrome (CRS) is a systemic (all your body) inflammatory response. It can be caused by certain medications, immunotherapy treatments (CAR-T cells), infections, or illnesses. It is a release of cytokines into your blood from your immune cells. This is a large and quick release that can happen after treatment with some types of immunotherapies, such as monoclonal antibodies and CAR-T cells. This release can overwhelm your body making it hard for your body to adjust.

What are the signs of cytokine release syndrome?

Signs and symptoms can range from mild to severe. The mild symptoms are:

  • Fever.
  • Fatigue.
  • Nausea.
  • Headache.
  • Rash.
  • Generalized aches and pain.

More severe symptoms are:

  • Fast heartbeat.
  • Low blood pressure.
  • Trouble breathing.
  • Confusion, dizziness, headache, and seizures.
  • Organ failure.
  • Higher than normal liver and kidney levels in your blood.
  • Changes in blood clotting.

The signs and symptoms of cytokine release syndrome are like signs and symptoms of other health issues, such as neutropenic fever and sepsis. It is important for your care team to rule out other illnesses that are not cytokine release syndrome.

How is cytokine release syndrome managed?

If you are having any signs or symptoms of cytokine release syndrome related to your immunotherapy treatment, you should be closely monitored. Your vital signs and lab values should be checked more often. Your symptoms will be managed as needed. Examples of treatments to manage symptoms include:

  • IV (intravenous, into a vein) fluids.
  • Oxygen.
  • Medication to manage your blood pressure, heart function, pain, and prevent seizures.
  • Blood products.

You may be given medications to lower your immune response, such as corticosteroids, tocilizumab, and siltuximab. These medications are immunosuppressive. This means they could interfere with the immunotherapy treatment you have received. Your care team will decide the best treatment for you before giving you these medications. If your reaction is severe, you may need to be treated in an intensive care unit (ICU) with a breathing tube or machines to help your heart work.

If you think you are having signs and symptoms of CRS, contact your provider right away.

Lipe, B. C., & Renaud, T. (2022). Siltuximab as a primary treatment for cytokine release syndrome in a patient receiving a bispecific antibody in a clinical trial setting. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 10781552221140320. Advance online publication. https://doi.org/10.1177/10781552221140320

NCI Dictionary of Cancer terms. National Cancer Institute. (n.d.). Retrieved March 13, 2023, from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/cytokine-release-syndrome

Pooja Toshniwal PahariaReviewed by Danielle Ellis. (2022, September 2). What are cytokines? News. Retrieved March 13, 2023, from https://www.news-medical.net/health/What-are-Cytokines.aspx

Riegler, L. L., Jones, G. P., & Lee, D. W. (2019). Current approaches in the grading and management of cytokine release syndrome after chimeric antigen receptor T-cell therapy. Therapeutics and clinical risk management, 15, 323–335. https://doi.org/10.2147/TCRM.S150524

Shimabukuro-Vornhagen, A., Gödel, P., Subklewe, M., Stemmler, H. J., Schlößer, H. A., Schlaak, M., Kochanek, M., Böll, B., & von Bergwelt-Baildon, M. S. (2018). Cytokine release syndrome. Journal for immunotherapy of cancer, 6(1), 56. https://doi.org/10.1186/s40425-018-0343-9

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