Cytokine Release Syndrome: Stages, Treatment, and Outlook

Medically Reviewed By Megan Soliman, MD
Was this helpful?

Cytokine release syndrome (CRS) is when your immune system has an exaggerated response to infection or immunotherapy. CRS can cause symptoms such as fever and rapid breathing, and range from mild to severe. Also known as cytokine storm or hypercytokinemia, CRS is the sudden release of cytokines into the body. Cytokines are small proteins the immune system makes to tell cells to perform specific functions.

In appropriate levels, cytokines are an important part of the immune response. However, the release of too many cytokines due to CRS can cause a potentially life threatening condition.

This article discusses cytokine release syndrome, including its symptoms, causes, and when to see a doctor. It also explains the diagnostic process, treatment, and prevention of CRS. Finally, this article also discusses the outlook of CRS.


A medical illustration demonstrating the symptoms of cytokine release syndrome.
Design by Mekhi Baldwin

Symptoms of CRS can affect a wide range of body systems and vary from mild to life threatening. Milder cases can also later become more severe over the course of a few days. As a result, close monitoring of even mild symptoms is essential.

If CRS occurs due to immunotherapy, the onset of CRS can happen within a few days. However, many cases occur up to a few weeks after starting therapy.

Mild symptoms may include:

It’s important to recognize the signs of CRS early to prevent serious complications. Serious cases of CRS can cause a large range of complications, such as:

These complications may cause serious symptoms, including:

If you experience any CRS symptoms after receiving immunotherapy, contact your doctor immediately.


The CRS grading system describes the severity of the reaction from least severe to most severe according to the following criteria:

grade 1

Grade 1 is a mild reaction and is not life threatening. If CRS results from immunotherapy, your doctors may continue with your treatment.

Treatment can be given to alleviate mild symptoms, such as headache or fever. 

grade 2

Grade 2 is a moderate reaction with some signs of organ dysfunction. Other symptoms at this stage require hospitalization for intravenous (IV) treatment or supplemental oxygen.

It’s also advisable for any immunotherapy infusion to stop at this stage.

grade 3

Grade 3 is a more severe reaction that also requires hospitalization to manage symptoms of organ dysfunction and low blood pressure. A person at this stage will need oxygen and other medications.

It may take longer for grade 3 CRS to respond to treatment.

grade 4

Grade 4 is a life threatening complication requiring hospitalization.

A person at this stage may need mechanical ventilation and medication to treat extremely low blood pressure. 


CRS occurs due to the body’s immune system overreacting, leading to the sudden release of large amounts of cytokines, which may cause the body’s cells to function improperly.

This usually happens in response to:

Immunotherapies are techniques that can increase or decrease immune activity. Doctors can prescribe them to treat conditions, such as:

  • cancer
  • immune deficiencies
  • autoimmune conditions
  • hypersensitivities
  • organ transplants
  • infections

Immunotherapy medications and treatments linked with CRS include but are not limited to:

  • anti-thymocyte globulin
  • CD28 superagonist TGN1412
  • dacetuzumab, also known as SGN-40
  • alemtuzumab (Campath, Lemtrada)
  • blinatumomab (Blincyto)
  • brentuximab (Adcetris)
  • lenalidomide (Revlimid)
  • nivolumab (Opdivo)
  • obinutuzumab (Gazyva)
  • oxaliplatin (Eloxatin)
  • rituximab (Rituxan)
  • tisagenlecleucel (Kymriah)

Contact your doctor to check whether your medication is associated with CRS.

Read more about immunotherapy for cancer.

Risk factors

Factors that can impact the likelihood and severity of CRS include:

  • the condition you are being treated for
  • how severe your underlying condition is
  • your general health
  • dosage of immunotherapy

Children may be at higher risk of experiencing CRS compared with adults.

The likelihood of experiencing CRS can also vary depending on the type of immunotherapy you receive.

T-cell-engaging cancer immunotherapies carry the highest risk of CRS. These therapies treat several types of cancers. Examples include blinatumomab and tisagenlecleucel.

When to see a doctor

If you’re taking immunotherapy medication, seek immediate medical care at the first symptom of CRS. This may include symptoms such as:

Some symptoms of mild CRS can resemble symptoms of infection. Due to this, it’s also important to contact your doctor immediately if you have any symptoms of illness that are not improving or are worsening. If you’re unsure about your condition, contact your doctor.

It’s also essential to seek immediate medical care for any severe symptoms, whether they could be due to CRS or not. Call 911 or seek emergency care for any of the following symptoms:

  • rapid heartbeat
  • difficulty breathing or rapid breathing
  • high fever
  • low blood pressure
  • confusion
  • difficulty with language
  • seizures
  • hallucinations
  • sleepiness, drowsiness, or difficulty waking
  • fainting or other changes in consciousness
  • discoloration of the skin

Learn more about the symptoms of low blood pressure.

Diagnosis and treatment

Symptoms of CRS can mimic several other medical conditions, such as:

  • infection
  • sepsis
  • adrenal insufficiency

To diagnose your condition, a doctor will review your medical history and conduct a physical exam. They may also order tests. Blood tests can help determine whether you have CRS.

Mild cases of CRS may only require monitoring and medications to help ease uncomfortable symptoms. Sometimes doctors may adapt your immunotherapy treatment to avoid further risks.

Doctors may prescribe medication to resolve the underlying illness if you have CRS due to infection.

More severe cases require several treatments, such as:


While some cases of CRS are unpredictable and unpreventable, there are ways to assess your risk level before starting immunotherapy.

Your doctor can discuss your risk level with you and go over all symptoms to watch for. During your first treatment, your medical team will closely monitor you for symptoms of CRS. 

People at high risk may benefit from taking an anti-cytokine therapy at the first sign of CRS to prevent severe progression.  

If you have questions about risk and prevention, contact your doctor.

Outlook and recovery

Your outlook can depend on the severity of your CRS reaction. 

People with mild cases typically recover with minimal care and can resume any necessary immunotherapy treatment. Those who experience more severe symptoms may take weeks or longer to recover. 

For some people, CRS can be fatal. However, early diagnosis and treatment can help slow or stop the progression of CRS.

Contact a doctor right away if you start to experience any symptoms of CRS.


Cytokine release syndrome (CRS) occurs when your immune system has an exaggerated reaction and releases too many cytokines into your bloodstream. This can happen in response to immunotherapy treatment or infection. 

CRS can range from mild to life threatening. People with mild cases may experience a headache or nausea, while those with severe cases may experience serious symptoms such as difficulty breathing and confusion.

Treatment depends on the severity of your condition and can include symptom management, IV therapy, and mechanical ventilation.

As CRS can start mildly and then worsen, contact a doctor immediately if you notice any symptoms of CRS.

Was this helpful?
Medical Reviewer: Megan Soliman, MD
Last Review Date: 2023 Feb 28
View All Symptoms and Conditions Articles
THIS TOOL DOES NOT PROVIDE MEDICAL ADVICE. It is intended for informational purposes only. It is not a substitute for professional medical advice, diagnosis or treatment. Never ignore professional medical advice in seeking treatment because of something you have read on the site. If you think you may have a medical emergency, immediately call your doctor or dial 911.