What is a Cytokine Storm?

June 29, 2021

Medically Reviewed By: Caron A. Jacobson, MD, MMSc

A cytokine storm is a severe immune system reaction to infection, autoimmune condition, or other disease, including some cancers. It occurs when the body produces extremely high levels of certain cytokines, which are proteins that raise or lower immune activity.

The deluge of cytokines into the bloodstream can result in severe inflammation across multiple bodily systems, organ dysfunction, and organ failure if not treated adequately.

Cytokine storm can be an especially dangerous result of COVID-19. The inflammation and fluid buildup in the lungs associated with the disease may deprive the body of sufficient oxygen and require patients to be placed on a mechanical ventilator.

What causes cytokine storm?

It isn’t clear why some patients develop cytokine storm while others with the same disease don’t, but it arises when the body overproduces certain immune-stimulating cytokines in response to an infection or other disease or to a medical treatment. The immune response normally operates under strict controls, ramping up to fight disease and standing down with the job is done. With cytokine storm, the response is out of proportion, resulting in impaired function and damaged tissue.

What conditions can trigger cytokine storm?

  • Macrophage activation syndrome, a severe complication of rheumatic disease in childhood, resulting in the uncontrolled activation and proliferation of T cells and macrophages — types of immune system cells
  • Some viral infections, such as the one responsible for COVID-19
  • Leukemia and lymphoma
  • Hemophagocytic lymphohistiocytosis, a rare disease in which white blood cells called histiocytes and lymphocytes attack other blood cells

What treatments can give rise to cytokine storm?

CAR T-cell therapy, a form of immunotherapy approved for the treatment of adults with B cell lymphoma, mantle cell lymphoma, and multiple myeloma, and children and young adults with acute lymphoblastic leukemia, is linked to cytokine release syndrome (CRS) — a form of cytokine storm — in some patients.

Patients who develop CRS may experience flu-like symptoms, such as high fever and/or chills, low blood pressure, or difficulty breathing. It usually arises within five days of patients’ being infused with CAR T cells. For most patients, the condition is mild enough that it can be managed with standard therapies such as acetaminophen and intravenous fluids.

In some cases, CRS is followed by a second wave of neurological side effects. These can include tremors, headaches, confusion, loss of balance, trouble speaking, seizures, and hallucinations. These symptoms generally subside in a few days, although some patients may require additional treatment.

What are the symptoms of cytokine storm?

  • High fever
  • Extreme fatigue
  • Difficulty breathing
  • A sharp drop in blood pressure
  • Blood clots
  • Nervous system problems such as headache, seizures, or even coma

Because some of these symptoms, such as fever and fatigue, can be caused by other disorders, it’s important to check with your doctor if they occur.

How is cytokine storm treated?

To treat patients with cytokine storm, doctors pursue a three-pronged strategy: keep vulnerable organs functioning, eliminate the triggers of the overactive immune response, and use agents that can moderate or reduce that response. Steroids are often a first choice of treatment to reduce inflammation.

As physicians have gained experience in treating CRS in patients who have undergone CAR T-cell therapy, they’ve developed effective methods of preventing it or reducing its severity.

Dana-Farber physician-researchers have launched studies to determine if treatments that have proven successful in cancer therapy can also help patients with severe cases of COVID-19. Steven Treon, MD, PhD, for example, opened a clinical trial of the drug ibrutinib — used in the treatment of Waldenström’s macroglobulinemia, a rare blood cancer — in patients with COVID-19. The trial follows several case reports in which ibrutinib appeared to protect against lung damage and respiratory distress caused by the coronavirus. The drug targets molecular pathways that are overactive in both Waldenström’s, where it affects the bone marrow, and the lungs of patients with COVID-19.