Cytokine Storm Explained for Cancer Patients: Symptoms, Tests, Treatment

If you are living with cancer, you may hear the words "cytokine storm" or "cytokine release syndrome (CRS)" in a clinic visit, in the hospital, or while reading about treatments like CAR T cell therapy. The phrase sounds frightening because it can be serious. The good news is that clinicians have learned a lot about how cytokine storm happens, how to recognize it sooner, and how to treat it more effectively than in the past.

This article explains a major review paper on the topic in plain English, with a focus on what matters most to cancer patients and families: what cytokine storm is, why it can happen in cancer or cancer treatment, what symptoms to watch for, what lab tests mean, and what treatments doctors may use.

Source note: The explanations here are based on the review "Cytokine storm" by Karki, Netea, Diorio, and Kanneganti in Nature Reviews Disease Primers .

First, what are cytokines?

Your immune system is your body's security team. It has:

A "fast response" group (often called the innate immune system), including cells like macrophages, monocytes, neutrophils, dendritic cells, natural killer (NK) cells, and mast cells.

A "specialized response" group (often called the adaptive immune system), including T cells and B cells.

These cells coordinate using chemical messages. Cytokines are some of the most important messages. You can think of cytokines like:

Text messages between immune cells ("Come here"; "Attack"; "Calm down"; "Make more defenses").

Alarm signals that tell nearby tissues something is wrong.

In a normal infection or injury, cytokines rise locally (in one area), do their job, and then fade as the problem resolves. Cytokines usually have short lifetimes in the body, which helps keep inflammation from spreading everywhere.

What is a cytokine storm?

"Cytokine storm" is not one single disease. It is a spectrum of clinical syndromes (different situations that can look similar) where:

Cytokine levels become unusually high in the bloodstream,

The immune response becomes overactivated instead of controlled,

And the inflammation starts damaging tissues and organs.

The paper emphasizes that cytokine storm can be triggered by many different underlying problems, including:

Infections (including sepsis and severe viral infections),

Auto-inflammatory and autoimmune diseases,

Genetic conditions that disrupt immune control (sometimes called "monogenic" causes),

Cancers (especially certain blood cancers),

Immune-modulating therapies (including CAR T cell therapy and other treatments that strongly activate immune cells).

In cancer care, you may hear "CRS" more often than "cytokine storm." CRS is a clinically defined syndrome caused by cytokine storm, and the term is commonly used for treatment-related cytokine storms (for example after CAR T cell therapy).

Why this matters in cancer

Cancer and cancer treatment can set the stage for cytokine storm in a few ways:

Some cancers can directly trigger powerful immune activation.

The review notes that malignancy-associated cytokine storm is a common cause of secondary HLH in adults, and it is often linked to lymphoma.

Some modern therapies intentionally supercharge the immune system to kill cancer.

CAR T cells and other T cell-engaging therapies can cause a surge of immune activation. Early CAR T trials reported very high rates of CRS; over time, earlier use (lower disease burden) and better management strategies reduced the rates of severe CRS.

Treatment can create signals that look like danger to the immune system.

When tumor cells are rapidly killed, they release "danger signals" (the paper calls these DAMPs, damage-associated molecular patterns). Those danger signals can activate immune sensors, which can drive more cytokine production.

How common is cytokine storm?

It is natural to ask, "How likely is this to happen to me?" The honest answer is: it depends a lot on the trigger, and it is hard to measure because different hospitals and studies use different definitions.

Here are some anchor points the paper gives:

Genetic ("primary") HLH is rare.

One study estimated about 1 in 100,000 children (Texas), while another reported about 1.2 per 1,000,000 children (Sweden).

Some inherited auto-inflammatory conditions linked to cytokine storm are also rare overall, but vary by region.

Cryopyrin-associated periodic syndromes were estimated around 1 to 3 per million people in one analysis.

Familial Mediterranean fever is much more common in certain populations (for example, about 1 in 500 to 1,000 in some regions), and far less common in others.

"Secondary" HLH (used as a clinical surrogate for non-genetic cytokine storm) is uncommon per condition, but not rare in aggregate.

A UK analysis estimated about 1 to 4 cases per 1,000,000 people in 2018, and noted the incidence increased over time, likely because clinicians recognize it more often now.

Infections can be a major driver, but exact rates of cytokine storm from infection are hard to pin down.

Sepsis is common globally (the paper cites ~677.5 cases per 100,000 people worldwide), but what fraction of sepsis meets criteria for cytokine storm is not well documented.

In a retrospective cohort of ICU patients with COVID-19, about 8.7% met criteria for secondary HLH.

In autoimmune and inflammatory diseases, cytokine storm can be a known complication in specific groups.

The paper notes macrophage activation syndrome (MAS) complicates about 10% of systemic juvenile idiopathic arthritis (with an additional 30-40% showing subclinical features in some studies).

MAS has also been reported in about 10% of childhood-onset systemic lupus erythematosus in some reports.

In adults, malignancy-associated cytokine storm/secondary HLH is often linked to blood cancers (especially lymphoma).

The paper notes roughly 40-60% of adult cytokine storm/secondary HLH cases are due to malignancy, and cites an incidence estimate of ~0.45 per 100,000 adults (2012-2018).

With CAR T cell therapy and similar T cell-engaging therapies, CRS is common, but severe CRS has become less common over time.

Early CAR T trials reported CRS in about 88-93% of patients, with higher rates of severe CRS.

In post-marketing surveillance, CRS rates are around ~50%.

The paper emphasizes that higher disease burden is linked to more severe CRS, and that improved management has reduced severe cases.

Bottom line: your individual risk depends on your cancer type, how active it is, what therapy you are receiving, and your overall health. Your oncology team is the best source for personalized risk.

The big idea from the paper: a self-amplifying loop

One of the most important explanations in the paper is that cytokine storm often becomes dangerous because it can "feed itself."

Here is the simplified version:

A trigger sets off the immune system.

A trigger can be a virus, bacteria, tissue damage, an autoimmune flare, a genetic defect, a tumor, or an immune therapy.

Immune sensors detect the trigger and switch on inflammatory programs.

The paper describes immune "sensors" that recognize patterns from microbes (PAMPs) or damage signals from injured cells (DAMPs). These sensors activate internal pathways that increase cytokine production.

Cytokines are released into tissues and (in severe cases) into the bloodstream.

Cytokines can be released through normal secretion or through inflammatory forms of cell death that cause cells to rupture.

Cytokines and damage signals then trigger nearby cells to become inflamed or die in a way that releases even more cytokines.

This is the "positive feedback loop": cytokines can drive more inflammation and inflammatory cell death, which releases more cytokines, which drives more inflammation, and so on.

The paper highlights a particular concept called PANoptosis, an inflammatory, lytic (cell-bursting) type of cell death that can help explain how the storm amplifies. You do not need to memorize that term to understand the message: when cells die in a messy, inflammatory way, they can spill out more signals that further inflame the neighborhood.

Two "danger signal" words you might see: PAMPs and DAMPs

The paper uses two helpful categories of triggers:

PAMPs (pathogen-associated molecular patterns): pieces of germs that immune cells recognize as "not self" (for example, parts of bacteria or viruses).

DAMPs (damage-associated molecular patterns): signals released by your own stressed or injured cells (for example, from tissue injury, severe inflammation, or rapid tumor cell death).

Both can flip immune alarms on. In cancer care, DAMPs are especially relevant when immune therapies cause rapid tumor killing: the dying tumor cells can release "danger" signals that wake up other immune cells and increase cytokine release.

A plain-English picture of PANoptosis

Cells can die in different ways. Some forms of cell death are "quiet" and tidy; others are "loud."

PANoptosis is a "loud" kind of cell death described in the paper:

It is triggered when immune sensors detect danger (microbial patterns, damage signals, or major disruptions inside cells).

It involves multiple cell-death machinery pathways working together.

The cell breaks open, spilling inflammatory contents (including cytokines and DAMPs).

Why does this matter? Because a bursting cell can spread the inflammatory alarm. The paper describes how this can happen not only inside the initially affected area, but also in neighboring cells ("paracrine" signaling), helping a local immune reaction become systemic.

The cytokines most often involved

The paper notes that the exact mix of cytokines differs depending on the trigger, but several show up repeatedly and seem to drive disease:

IL-1 family cytokines (including IL-1 beta and IL-18),

IL-6,

TNF,

Interferon-gamma (IFN-gamma),

And others depending on context.

The paper also discusses evidence that TNF and IFN-gamma can act together in a particularly harmful way, helping drive the inflammatory cell-death-and-cytokine loop.

Who makes the cytokines?

The paper describes cytokine storm as a network problem. Many cell types can be involved:

Innate immune cells often start the process:

Macrophages and monocytes are major early sources of IL-1 beta, IL-6, and TNF.

NK cells and certain T cell-like innate cells can contribute IFN-gamma and TNF in some viral settings.

Neutrophils can worsen tissue injury through NETs (neutrophil extracellular traps), which can behave like damage signals and promote clotting problems.

Adaptive immune cells can amplify and sustain the storm:

Certain activated helper T cells can produce IFN-gamma and IL-17, which can activate macrophages and recruit more inflammatory cells.

Cytotoxic T cells can add inflammatory cytokines and (by killing infected or abnormal cells) indirectly increase damage signals.

B cells can contribute indirectly, especially in autoimmune conditions, by making antibodies that form immune complexes and activate other immune cells.

Non-immune cells matter too:

Blood vessel lining cells (endothelial cells), platelets, and tissue cells can contribute to inflammation, vascular leak, and clotting problems as the storm progresses.

In cancer therapy-induced cytokine storm, engineered immune cells (like CAR T cells) are part of this network. They can initiate a burst of tumor killing and immune activation, and then the patient's own innate immune cells can contribute large amounts of cytokines.

How cytokine storm typically progresses over time

The paper describes four overlapping phases. The exact timeline differs by person and trigger, but the pattern is useful:

Onset (often hours to day 1-2)

Early cytokine release begins.

Symptoms can be non-specific: fever, chills, feeling unwell, fast heart rate.

Amplification (often days 2-5)

More immune cells are recruited and activated.

Inflammatory cell death and cytokine feedback can accelerate.

Blood vessels can become leaky; oxygen levels can begin to drop.

Peak/crisis (often days 5-10 in some settings)

The body can develop serious complications:

Low blood pressure (shock),

Low oxygen and lung injury (ARDS),

Abnormal blood counts (cytopenias),

Clotting problems (coagulopathy),

Multi-organ dysfunction.

Resolution or failure (day 10 onward in some settings)

With effective treatment and recovery, inflammation contracts.

In severe cases, the immune system can swing into "immune paralysis" (an exhausted, suppressed state), which can raise the risk of secondary infections.

For patients and families, the key message is timing: earlier recognition and treatment can prevent the most dangerous complications.

What it can feel like: symptoms and organ effects

The paper lists a wide range of symptoms because cytokine storm affects the whole body. Early symptoms are often vague, which is part of what makes it dangerous.

Common early or general symptoms can include:

Persistent fever (often the most consistent early sign),

Chills, sweats,

Fatigue, weakness, loss of appetite,

Headache,

Muscle aches or joint pains,

Nausea or diarrhea,

Confusion, agitation, or mood changes (especially concerning).

As it worsens, symptoms can reflect organ involvement:

Lungs: shortness of breath, cough, low oxygen, ARDS.

Heart and blood pressure: fast heart rate, low blood pressure, arrhythmias, heart strain.

Brain: "brain fog," delirium, seizures, encephalopathy.

Liver: jaundice, liver injury (abnormal liver enzymes).

Kidneys: low urine output, fluid retention, kidney injury.

Blood vessels and blood: capillary leak (swelling), clotting abnormalities, bleeding or micro-clots, abnormal blood counts.

When to treat this as urgent

Because cancer patients may have multiple reasons for fever or fatigue (infection, treatment effects, dehydration, anemia, etc.), it is not always obvious what is happening at home. But urgent evaluation is especially important if you have:

Trouble breathing, new/worsening shortness of breath, or low oxygen readings,

New confusion, severe sleepiness, fainting, or seizures,

Persistent high fever that does not respond the way your team expects,

Very low blood pressure symptoms (dizziness, collapse),

Chest pain, severe rapid heartbeat, or new irregular heartbeat,

Rapid swelling, severe weakness, or inability to keep down fluids.

If you are on CAR T cell therapy or another immune-activating therapy, your care team will usually give you specific instructions about what to report immediately. Follow those instructions even if you are not sure the symptom is related.

How doctors look for cytokine storm: why lab tests matter

The paper makes an important point: there is no single perfect biomarker for cytokine storm today.

Instead, clinicians use a combination of:

Your symptoms,

Your underlying condition and recent treatments,

And lab patterns that suggest systemic inflammation and immune overactivation.

Common lab findings mentioned in the paper include:

CRP (C-reactive protein): an inflammation marker made by the liver; often rises with severity.

Blood counts:

Some people have low white cells (leukopenia) or high white cells (leukocytosis),

Low platelets (thrombocytopenia),

Anemia.

Clotting-related changes:

Elevated D-dimer,

Low fibrinogen in some cases,

Signs of (sub)clinical disseminated intravascular coagulation (a dangerous clotting disorder).

High triglycerides (hypertriglyceridemia) in some syndromes.

Liver enzymes (transaminases) may rise, especially if hepatitis-like inflammation occurs.

Other assessments the paper mentions (depending on the situation) include:

Imaging to look for an enlarged liver, spleen, or lymph nodes (clues that organs are involved).

Bone marrow evaluation in selected cases, although the paper notes that bone marrow findings like hemophagocytosis are not perfectly sensitive or specific, and biopsies are not always done.

Ferritin: one clue clinicians take seriously

Ferritin is a protein that stores iron. In cytokine storm, ferritin can become very high, partly because activated macrophages (and other cells) release it during intense inflammation. The paper notes that there is not one universal ferritin cutoff for cytokine storm, but very high levels should prompt clinicians to consider it; for example, in Still disease-associated MAS, median ferritin levels above 5,000 ng/mL have been reported.

Cytokine measurements (when available)

In some settings, clinicians can measure cytokines or related pathway markers, such as:

IL-6 and soluble IL-2 receptor (sCD25) in CAR T-associated cytokine storm,

IFN-gamma activity markers like CXCL9,

IL-18 (which can drive IFN-gamma) in MAS/Still disease-related syndromes,

IL-17 in Kawasaki disease-related syndromes.

The paper stresses that there is no single standard "cytokine profile" that reliably predicts cytokine storm across all causes. That is why clinical judgment and early recognition remain so important.

Why diagnosis can be difficult (and why it matters)

Many conditions can look similar at first:

Infection and sepsis,

A flare of autoimmune disease,

A reaction to a new immune therapy,

Progression of an underlying cancer.

Because the treatments can differ (for example, treating a bacterial infection aggressively versus treating a therapy-induced cytokine storm), clinicians work hard to identify the trigger while also stabilizing the patient. The paper emphasizes the importance of a complete infection work-up in suspected cases and assessing organ function.

Practical questions to ask your cancer team (especially before CAR T or T cell-engaging therapy)

If you are starting a therapy that carries CRS risk, consider asking:

"What symptoms should I report immediately, even overnight?"

"Who do I call after hours, and when should I go straight to the emergency department?"

"If I develop a fever, should I treat it at home first or call right away?"

"How will you monitor me for CRS (vitals, labs), and for how long?"

"What treatments does your team typically use first if CRS happens (for example, IL-6 blockers, steroids), and what side effects should I expect?"

"How will you watch for neurologic side effects, and what should my caregiver look for?"

These questions are not about self-diagnosing; they are about making sure you and your caregiver have a clear, rehearsed plan.

How cytokine storm is treated: the major approaches

Treatment depends on the cause (infection vs autoimmune vs cancer vs therapy-related) and on how sick the patient is. The paper highlights three big goals:

Treat the trigger (for example, infection, autoimmune flare, cancer-related driver, or therapy-related mechanism).

Support vital organs while the storm is controlled (oxygen, blood pressure support, ICU care if needed).

Calm the harmful immune inflammation before it causes irreversible organ injury.

In real life, these steps often happen at the same time. For example, a patient may receive oxygen and blood pressure support while clinicians run tests to rule out infection and decide whether to start cytokine-targeted therapy. This "parallel work" is one reason cytokine storm care often happens in a hospital.

Below are the main anti-inflammatory and immune-targeted tools discussed in the paper.

1) Glucocorticoids (steroids)

Steroids (like methylprednisolone or dexamethasone) are powerful anti-inflammatory medications that reduce multiple inflammatory pathways and cytokine production.

The paper notes:

Steroids are an important part of treatment for many cytokine storm syndromes.

They may be particularly beneficial when cytokine storm is driven by autoimmune disease.

In therapy-related cytokine storm (like after CAR T), clinicians may prefer more targeted approaches because steroids can sometimes reduce the desired anti-cancer immune effect and can increase infection risk.

2) Cytokine blockers (targeted antibodies or receptor blockers)

These treatments aim to neutralize one specific cytokine pathway that is fueling inflammation.

IL-1 pathway blockers:

Anakinra (an IL-1 receptor antagonist) is highlighted as a key option because it has a short half-life (which can be useful when balancing infection risk).

The paper describes evidence supporting anakinra in several cytokine storm settings, including certain COVID-19 hyperinflammation scenarios, Still disease-associated cytokine storm, and ongoing trials in sepsis-associated cytokine storm.

Canakinumab (anti-IL-1 beta) is another option, but the paper notes drawbacks such as longer half-life and other limitations.

IL-6 pathway blockers:

Tocilizumab (anti-IL-6 receptor) is commonly used in CAR T-associated CRS, where IL-6 is an important driver of symptoms.

The paper notes a key limitation: tocilizumab is not known to cross the blood-brain barrier well, so it may not help certain neurotoxicity complications.

For COVID-19-related hyperinflammation, IL-6 blockade has shown mixed results across trials; some large trials showed benefit in certain severely ill patients, while others did not improve mortality.

IFN-gamma blockade:

Emapalumab (anti-IFN-gamma) is used for certain severe cases, such as primary HLH that is refractory to conventional therapy, and in some cases of Still disease-associated cytokine storm that do not respond to high-dose steroids.

Because IFN-gamma is important for fighting infections, careful monitoring for infections is important.

TNF blockade:

The paper discusses TNF-targeted therapies cautiously: some small reports suggest benefit in certain contexts, but other studies show increased infection risk and impaired host defense.

3) JAK inhibitors (blocking a shared signaling hub)

Many cytokines transmit their messages inside cells through a pathway involving proteins called JAKs. The paper notes that:

JAK inhibitors may have broader effects because they can dampen signaling from multiple cytokines.

Ruxolitinib (JAK1/JAK2 inhibitor) has shown benefit in children with HLH.

Baricitinib has shown efficacy in COVID-19.

4) Etoposide (in certain severe syndromes)

Etoposide is a chemotherapy drug that has a role in treating primary HLH and some severe or refractory cytokine storm syndromes. The paper notes that it may help by depleting activated T cells in hyperinflammatory settings, but its effect on survival can vary and it is typically reserved for specific clinical scenarios.

Why timing matters: treating early vs treating late

The paper repeatedly returns to an important clinical reality:

Cytokine storm can escalate quickly.

Once organs are failing, treatment becomes harder and risks increase.

That is why clinicians emphasize early recognition and early treatment. It is also why patients on high-risk therapies (like CAR T) are monitored closely, often in the hospital around the time when symptoms typically appear.

What prevention can (and cannot) do

Not all cytokine storms are preventable, but the paper discusses strategies that might lower risk in some contexts:

Preventing infection is important because infections are a common trigger. (This includes basic precautions and, for many cancer patients, following the infection-prevention plan your team gives you.)

Some experimental and retrospective evidence suggests that lowering catecholamine surges (stress hormones) with certain medications may reduce inflammatory cytokine responses in specific settings, but this is not a universal or standard prevention approach and needs clinical judgment.

For cancer patients, the most practical "prevention" usually looks like:

Knowing your risk based on your treatment and disease,

Following your team's monitoring plan,

Reporting symptoms early,

And having a clear plan for after-hours contact and emergency evaluation.

Life after cytokine storm: what is known about quality of life

The paper notes that long-term quality-of-life research is limited.

Some findings it highlights:

In one study of COVID-19 hyperinflammation syndrome, quality-of-life measures did not show an impact at 3 and 6 months.

In children diagnosed with HLH, quality of life was lower than healthy controls in the first year, but by 5 years it was not statistically different from peers.

The overall message is cautious optimism: recovery can be substantial, but more research is needed, and experiences differ depending on the cause of the cytokine storm and the severity of illness.

What the future may bring (the paper's outlook)

The review describes several promising directions:

Better biomarkers and clearer diagnostic criteria so treatment can start earlier and more confidently.

Improved models that mimic the human condition more accurately, helping treatments translate from the lab to the clinic.

Combination approaches (blocking more than one pathway) when the biology suggests synergy.

The paper points to preclinical evidence that blocking both TNF and IFN-gamma together can improve outcomes in certain models.

It also highlights the idea that combining IL-6 blockade (tocilizumab) with IL-1 blockade (anakinra) might help in CAR T-associated cytokine storm, especially when neurotoxicity is a concern.

Use of AI and machine learning to analyze large patient datasets and identify patterns and thresholds that can guide rapid diagnosis and individualized treatment.

Key takeaways (for cancer patients and families)

Cytokine storm is a dangerous form of immune overreaction, not a single disease.

In cancer, it can be linked to the cancer itself (especially some blood cancers) or to immune-activating treatments (especially CAR T and other T cell-engaging therapies).

Early symptoms can look like many other problems (fever, fatigue, confusion), so context and close monitoring matter.

There is no single test that diagnoses cytokine storm; clinicians use symptom patterns plus labs like CRP, ferritin, blood counts, and clotting markers, sometimes paired with cytokine/pathway testing.

Treatment usually combines supportive care plus medicines that calm the immune system (steroids, cytokine blockers like IL-1 or IL-6 inhibitors, IFN-gamma blockade in selected cases, JAK inhibitors, and other therapies depending on syndrome).

Earlier recognition and treatment can be lifesaving.

Plain-English glossary (quick definitions)

Cytokines: small proteins that immune cells use to communicate and coordinate inflammation.

Cytokine storm: a harmful state of extreme, widespread immune activation with very high cytokine signaling that can injure organs.

CRS (cytokine release syndrome): a clinical syndrome caused by cytokine storm, often used for therapy-related cases (for example, CAR T-related CRS).

HLH (hemophagocytic lymphohistiocytosis): a severe immune dysregulation syndrome where immune cells stay activated, cytokines rise, and organs can fail; can be genetic ("primary") or triggered by other conditions ("secondary").

MAS (macrophage activation syndrome): a rheumatology-linked subtype of secondary HLH/cytokine storm.

PAMPs / DAMPs: "danger patterns" from germs (PAMPs) or from injured/stressed cells (DAMPs) that can activate immune alarms.

Ferritin: an iron-storage protein; extremely high levels can be a clue to cytokine storm syndromes.

CRP: a liver-made protein that rises with inflammation; often used to track severity and response.

D-dimer / fibrinogen: blood clotting-related tests that can change when inflammation disrupts coagulation.

ARDS: severe inflammatory lung injury that makes it hard to get oxygen into the blood.

JAK inhibitors: drugs that block a common signaling pathway used by multiple cytokines (examples in the paper include ruxolitinib and baricitinib).

Citation

Karki R, Netea MG, Diorio C, Kanneganti T-D. Cytokine storm. Nature Reviews Disease Primers. 2026;12:1. doi:10.1038/s41572-025-00677-4