Cytokine Release Syndrome (CRS)

Cytokine release syndrome (CRS) occurs when your immune system releases large amounts of cytokines into your bloodstream. The condition can happen if you have immunotherapy.

Cytokines are proteins that are part of a healthy immune system. They help control the growth and activity of your blood cells and immune cells. But a flood of cytokines may cause widespread inflammation. This can lead to serious and sometimes life-threatening conditions, including organ failure.

Cytokine release syndrome falls under the medical condition cytokine storm.

Symptoms of cytokine release syndrome

Cytokine release syndrome symptoms can be mild. You may feel like you have the flu. But the syndrome may affect different areas of your body, causing symptoms like:

• Chills and high fever
• Confusion and dizziness
• Diarrhea
• Difficulty swallowing
• Headaches
• Joint and muscle pain
• Nausea and vomiting
• Skin rash
• Tiredness

Cytokine release syndrome causes

The syndrome happens when your immune system overreacts and releases large amounts of cytokines. Immunotherapy for cancer, particularly CAR-T cell therapy and bispecific antibodies, is the most common trigger.

Risk factors

Having an autoimmune disease or certain genetic conditions that affect your immune system may increase your risk. Hemophagocytic lymphohistiocytosis (HLH) is an example of a genetic condition that can lead to cytokine release syndrome.

Complications of this syndrome

Cytokine release syndrome can cause severe inflammation in your kidneys, liver or lungs. But it may also damage your blood vessels or heart. Without prompt treatment, CRS may cause serious medical issues. Some may be life-threatening, including:

• Capillary leak syndrome
• Cardiomyopathy and heart failure
• Kidney failure
• Liver failure
• Lung failure and very low oxygen levels

How doctors diagnose this syndrome

Healthcare providers diagnose CRS in different ways depending on the cause. For example, if you receive immunotherapy, your provider will watch for CRS symptoms. Those symptoms may show up within 24 hours or up to two weeks after your treatment. If you develop symptoms, your provider may do tests, including:

• Complete blood count (CBC)
• Cytokine levels
• C-reactive protein test and other tests to check inflammation levels
• Kidney and liver function

Cytokine release syndrome grades

Cytokine release syndrome grades range from 1 to 4. The higher the number, the more serious the condition. Your healthcare provider will consider the following issues to establish a grade for your condition:

• You have a high fever, low blood pressure or a fast heartbeat.
• They need to take steps to keep your vital signs stable.
• You need mechanical ventilation.
• You have organ failure symptoms, like weakness and fast, shallow breathing.

Cytokine release syndrome treatment

Your treatment will vary depending on the reason why you have CRS. For example, treatment for severe CRS from immunotherapy may include:

• Corticosteroids to reduce inflammation
• Medication that targets specific cytokines, like siltuximab (Sylvant^®), tocilizumab (Actemra^®) and anakinra (Kineret^®)
• Medication for very low blood pressure
• Mechanical ventilation

Recovery time

Your recovery time depends on your situation. People with mild CRS symptoms after immunotherapy usually recover within one to two weeks. Your recovery may take longer if an infection causes CRS.

When should I seek care?

Contact your healthcare provider if immunotherapy causes a fever or other CRS symptoms. The condition can worsen quickly. This increases your risk of life-threatening complications. It’s important that you get medical care right away.

What can I expect if I have CRS?

That depends on the cause and your symptoms. For example, you may feel better within a few days after treatment for mild CRS symptoms from immunotherapy. It will take longer to recover from severe CRS.