Cytokine Release Syndrome Symptoms Causes Treatments Health ConditionsFeaturedBreast CancerIBD MigraineMultiple Sclerosis (MS)Rheumatoid ArthritisType 2 DiabetesSponsored TopicsArticlesAcid RefluxADHDAllergiesAlzheimer's & DementiaBipolar DisorderCancerCrohn's DiseaseChronic PainCold & FluCOPDDepressionFibromyalgiaHeart DiseaseHigh CholesterolHIVHypertensionIPFOsteoarthritisPsoriasisSkin Disorders and CareSTDsDiscoverWellness TopicsNutritionFitnessSkin CareSexual HealthWomen's HealthMental HealthSleepOriginal SeriesFresh Food FastDiagnosis DiariesYou’re Not AlonePresent TenseVideo SeriesYouth in FocusHealthy HarvestNo More SilenceFuture of HealthPlanHealth ChallengesMindful EatingSugar SavvyMove Your BodyGut HealthMood FoodsAlign Your SpineFind CarePrimary CareMental HealthOB-GYNDermatologistsNeurologistsCardiologistsOrthopedistsLifestyle QuizzesWeight ManagementAm I Depressed? A Quiz for TeensAre You a Workaholic?How Well Do You Sleep?Tools & ResourcesHealth NewsFind a DietFind Healthy SnacksDrugs A-ZHealth A-ZConnectFind Your Bezzy CommunityBreast CancerInflammatory Bowel DiseasePsoriatic ArthritisMigraineMultiple SclerosisPsoriasisFollow us on social mediaShopProducts by ConditionInsomniaStress ReliefBack PainNeck PainSleep ApneaHot SleepersAllergiesPain ReliefProduct ReviewsVitamins & SupplementsSleepMental HealthNutritionAt-Home TestingCBDMen’s HealthWomen’s HealthHealth ConditionsDiscoverPlanConnectShopSubscribe

Cytokine Release Syndrome Symptoms Causes Treatments

Medically reviewed by William C Lloyd III, MD, FACS — By S. Behring on October 5, 2022Immunotherapy can help your body fight cancer. This development in cancer treatment has helped improve cancer treatment outlook in recent years. However, sometimes immunotherapy treatments can cause your immune system to overreact. This is called cytokine release syndrome, and it can lead to inflammation and toxicity throughout the body. Some cases of cytokine release syndrome are mild and easily treated, but others can be fatal. Treatment depends on the severity. It often includes immunosuppressive medications and oxygen support. This article will provide you with information about what causes cytokine release syndrome and how you can recognize the symptoms, as well as which types of treatment might be best for you, depending on the severity of your situation and whether you can take immunosuppressive medications.

What is cytokine release syndrome

Cytokine release syndrome is a set of symptoms that can develop as a side effect of immunotherapy treatment or as a response to infection. Many early hospitalizations for severe COVID-19 were complicated by cytokine release syndrome, according to a June 2020 study. Cytokines are a type of messenger protein that helps direct immune responses. Very high levels of cytokines can cause the immune system to kick in throughout the entire body, resulting in inflammation and a wide range of symptoms. Many cases of cytokine release syndrome are mild and cause symptoms such as fever and nausea. However, in severe cases, cytokine response syndrome can lead to possible organ failure and even death.

What causes this syndrome

Cytokines are important for your immune system. They tell your immune system how to respond to possible threats and help control the action and growth of immune and blood cells. Cytokine release syndrome can occur when immunotherapy causes too many cytokines to be released throughout the body. It can also happen when your body is responding to infection and makes too much cytokine. High levels of cytokines in the bloodstream can cause the immune system to go into overdrive, which can cause inflammation throughout the body. Certain types of immunotherapy increase the risk of cytokine release syndrome:Blinatumomab: Children receiving blinatumomab (Blincyto) monoclonal antibody treatment have an increased risk.Ttisagenlecleucel: Children receiving tisagenlecleucel (Kymriah) CAR T-cell immunotherapy are at a higher risk.Rituximab: The risk is higher for people of all ages receiving rituximab (Rituxan) monoclonal antibody treatment. Additionally, some groups undergoing immunotherapy are at higher risk. These include people who: are ages 65 and overlive in group living or nursing care facilitieslive with any type of diabeteshave heart diseasehave any underlying health conditions that affect the immune systemhave obesity

Are there different stages of cytokine release syndrome

Doctors group cases of cytokine release syndrome into stages based on the severity of symptoms. There are four cytokine release syndrome stages, or grades. Higher stages are for more serious symptoms. Factors that are used to determine staging include:severity of symptomsblood pressure, heart rate, respiration rate, and other vital signsnumber of medical interventions needed a person’s ability to breathe on their ownpresence of organ toxicity or damage Not every medical facility uses the exact same stages or grading guidelines. However, general stages are broken down as:Stage 1: This stage causes mild symptoms that respond to treatment.Stage 2: In this stage, people experience moderate symptoms that require treatment. Organ toxicity is present, and supplemental oxygen might be needed. Stage 3: In this stage, severe symptoms that require aggressive treatment occur. Organ toxicity is present, supplemental oxygen is needed, and blood pressure is very low. Stage 4: This stage causes life threatening symptoms. People in stage 4 might require a ventilator and will have significant organ toxicity.

Symptoms of cytokine release syndrome

The symptoms of cytokine release syndrome vary depending on the stage and on the organ systems affected. Some people will experience mild symptoms. Other cases of cytokine release syndrome can be fatal. Genera symptoms of cytokine release syndrome include:feverchillsfatigueloss of appetitenauseavomitingheadachemuscle painjoint painskin rash If cytokine release syndrome progresses to later stages, symptoms might include:low blood pressurerapid heart rateswelling in the legs and feetconfusiondizzinessdifficulty communicatingloss of coordination and fine motor skillsseizurehallucinationschronic coughshortness of breathdecreased blood oxygen level

Can you prevent this syndrome by avoiding immunotherapy

Cytokine release syndrome isn’t always a side effect of immunotherapy. It can also be caused by infections. This means that although immunotherapy greatly increases the risk, people who’ve never received immunotherapy can also develop cytokine release syndrome. It’s not possible to 100% prevent this syndrome. However, reducing your dose of immunotherapy medication can lower your risk. Consult your doctor about immunotherapy and your individual risks. They can prescribe the specific dosage or specific type of immunotherapy treatment that carries the lowest risk for you.

How do you treat this

Treatment of cytokine release syndrome varies depending on the stages and symptoms. Mild cases in the early stages will have a very different treatment course than severe, late-stage cases. Additionally, the overall health of the person and the current status of their cancer treatment can play a role in how cytokine release syndrome is treated. Treatment might include:Monitoring: People who are at risk for cytokine release syndrome are often monitored for symptoms that could signal the condition. This typically includes treatment with immunosuppressant medications to prevent cytokine release syndrome and lab testing to watch for rising cytokine levels.Symptom management: Treatment for cytokine release syndrome typically involves treating symptoms. This might involve medications to help support your heart function, regulate your blood pressure, manage pain, and prevent seizures.Oxygen support: Many people experiencing cytokine release syndrome are treated with supplemental oxygen. In severe cases, a ventilator might be needed. Blood transfusions: Blood transfusions can help improve symptoms and increase blood oxygen levels.Immune-system suppression: Severe cytokine release syndrome is treated with corticosteroids and other immunosuppressive medications, including medications, such as tocilizumab and siltuximab, that block cytokine release.

Takeaway

Cytokine release syndrome is an immune system overresponse that can occur as the result of immunotherapy or infection. It happens when an immune system communication protein called cytokine is overproduced. This leads to inflammation throughout the body. In mild cases, cytokine release syndrome causes symptoms such as fever, headache, and nausea. In severe cases, cytokine release syndrome can lead to organ failure and death. Treatment for cytokine release syndrome depends on the severity but might include immunosuppressive medications, oxygen support, blood transfusions, and medications for symptom management. Last medically reviewed on October 5, 2022

How we vetted this article

SourcesHistoryHealthline has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions, and medical associations. We avoid using tertiary references. You can learn more about how we ensure our content is accurate and current by reading our editorial policy.Cytokine release syndrome. (n.d.).
cancer.gov/publications/dictionaries/cancer-terms/def/cytokine-release-syndromeCytokine release syndrome (2021).
sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/cytokine-release-syndromeMorris EC, et al. (2022). Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy.
nature.com/articles/s41577-021-00547-6Price CC, et al. (2020). Tocilizumab treatment for cytokine release syndrome in hospitalized patients with coronavirus disease 2019.
journal.chestnet.org/article/S0012-3692(20)31670-6/fulltextShimabukuro-Vornhagen A, et al. (2018). Cytokine release syndrome.
ncbi.nlm.nih.gov/pmc/articles/PMC6003181/Tvedt THA, et al. (2021). Cytokine release syndrome in the immunotherapy of hematological malignancies: the biology behind and possible clinical consequences.
ncbi.nlm.nih.gov/pmc/articles/PMC8585070/Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Current Version Oct 5, 2022 By S. Behring Edited By Mike Hoskins Medically Reviewed By William C Lloyd III, MD, FACS Copy Edited By Chris Doka Share this articleMedically reviewed by William C Lloyd III, MD, FACS — By S. Behring on October 5, 2022

Read this next

Immunotherapy for Cancer and the COVID Vaccine: Safety, Effectiveness, and Schedule We review what people who take immunotherapy for cancer need to know about the COVID vaccines.READ MOREDoes Social Distancing Impact the Immune System?Medically reviewed by Danielle Hildreth, RN, CPT Social distancing is effective in helping to reduce the spread of disease, but it can also have negative impacts on emotional and mental health.READ MOREEverything You Need to Know About Severe Combined Immunodeficiency (SCID) SCID is a very rare but serious congenital condition. Learn about its causes, symptoms, treatment, and outlook.READ MORESwollen Lymph Nodes in the Groin: What Does It Mean?Medically reviewed by Alana Biggers, M.D., MPH Swollen lymph nodes in the groin could be due to various conditions, from sexually transmitted infections to athletes foot or even cancer. Here's what…READ MOREWhat to Know About IVIG (Intravenous Immunoglobulin) Infusions IVIG infusions provide your immune system with the antibodies it needs to help fight off infections. They can also help decrease inflammation and…READ MOREWhat Is Complete Decongestive Therapy? Complete decongestive therapy is an effective, noninvasive treatment for lymphedema. We'll review what it involves and answer some common questions.READ MOREDoes Exercise Boost Immunity?By Sara Lindberg Can exercise boost your immunity? It depends. Here's what to know about exercise as a catalyst of your body's immune response.READ MOREMonoclonal Antibody Treatment for COVID-19 Monoclonal antibody treatment can help your body fight COVID-19. Learn how it works and who should have it.READ MORE