Interleukin-6 (IL-6) Test: Role, High/Low Levels, Functions & Medical Interpretation
What Is Interleukin-6 (IL-6)?
Interleukin-6 (IL-6) is a cytokine—a small signaling protein that helps immune cells communicate and coordinate responses during injury, infection, or inflammation. Unlike many immune molecules that have only one type of action, IL-6 can behave in both pro-inflammatory and anti-inflammatory ways, depending on the condition and the cells involved.
During infections, IL-6 rises quickly to help the body fight harmful microorganisms. It stimulates fever, activates immune cells, and signals the liver to produce inflammation-related proteins. In chronic conditions such as autoimmune disorders, metabolic diseases, or obesity, IL-6 may remain persistently elevated and contribute to long-term inflammation. Extremely high IL-6 levels may indicate severe illness, such as sepsis, cytokine storm, or serious viral disease.
Because IL-6 rises early in inflammation, doctors use this test to assess the severity of infections, evaluate autoimmune activity, monitor cancer-related inflammation, and determine the risk of cytokine storms.
Where Is IL-6 Produced in the Body?
IL-6 is produced by many different tissues, making it a widespread and versatile immune messenger. When the body senses danger—whether from infection, injury, or stress—various cells release IL-6 to alert the immune system.
Major IL-6-producing cells include:
- Macrophages and monocytes: Produce IL-6 rapidly during bacterial or viral infections.
- T cells and B cells: Release IL-6 during immune activation or autoimmune reactions.
- Fibroblasts: Respond to tissue damage by producing IL-6.
- Endothelial cells: Release IL-6 from the lining of blood vessels during inflammation.
- Skeletal muscle: Produces IL-6 during physical activity or muscle injury.
- Adipose (fat) tissue: A major chronic source of IL-6 in obesity and metabolic syndrome.
Because so many tissues can produce IL-6, levels may rise in a wide variety of health conditions—not only infectious diseases but also chronic inflammatory, metabolic, or malignant disorders.
Main Functions and Importance of IL-6
1. Helps Fight Infections
IL-6 is one of the earliest cytokines to rise during infection. It stimulates immune cells, enhances pathogen recognition, and helps the body mount a rapid defense.
2. Converts B Cells Into Antibody-Producing Cells
IL-6 helps B cells mature into plasma cells. These cells produce antibodies that protect the body from future infections.
3. Activates T Cells
T cells are essential for regulating immune responses. IL-6 influences their activation and helps balance different immune pathways, especially during viral infections.
4. Stimulates the Liver to Produce Acute-Phase Proteins
IL-6 triggers the liver to produce inflammation-related proteins such as:
- C-Reactive Protein (CRP)
- Fibrinogen
- Serum Amyloid A
These proteins are used as medical markers to evaluate infection severity, inflammation, and sepsis risk.
5. Controls Fever and Inflammatory Responses
IL-6 interacts with the brain’s temperature-regulation center to produce fever, which helps the body fight infection. It also promotes inflammation to support healing.
6. Regulates Blood Cell Formation and Bone Metabolism
IL-6 helps control:
- Hematopoiesis (new blood cell production)
- Bone resorption and remodeling
Imbalances may contribute to anemia or bone-related disorders in chronic inflammation.
7. Major Player in Cytokine Storms
Very high IL-6 levels are a hallmark of cytokine storms—dangerous immune overreactions seen in:
- Severe COVID-19
- Dengue shock syndrome
- Influenza complications
- CAR-T therapy–related cytokine release syndrome
These conditions can lead to organ damage and require urgent medical care.
Causes of Low IL-6 Levels
1. Normal Healthy State
Healthy individuals typically have very low or undetectable IL-6 levels.
2. Immune Suppression
Low IL-6 may be associated with:
- Immunosuppressive medications (steroids, chemotherapy)
- Primary immune deficiencies
- Certain chronic illnesses that reduce immune activity
Low IL-6 does not usually cause symptoms itself, but it may indicate a poorly responsive immune system.
Symptoms of Low IL-6 Levels
Symptoms are due to underlying immune weakness rather than IL-6 deficiency itself:
- Frequent infections
- Slow healing of wounds
- Unusual tiredness
- Weak fever response
- Longer recovery time from illnesses
Causes of High IL-6 Levels
1. Infections
Both mild and severe infections can elevate IL-6:
- Bacterial infections (pneumonia, urinary infections)
- Viral infections (COVID-19, influenza, hepatitis, dengue)
- Fungal or parasitic diseases
2. Sepsis and Septic Shock
IL-6 levels may increase dramatically (often >100 pg/mL or much higher), indicating life-threatening infection.
3. Autoimmune Diseases
Chronic autoimmune inflammation strongly activates IL-6, especially in:
- Rheumatoid arthritis
- Systemic lupus erythematosus (SLE)
- Inflammatory bowel disease (Crohn’s disease, ulcerative colitis)
4. Severe Viral Illness
Cytokine storms caused by aggressive viral infections can produce dangerously high IL-6.
5. Cancers
Some cancers, especially blood-related cancers such as lymphoma and multiple myeloma, can increase IL-6 levels.
6. Obesity and Metabolic Syndrome
Fat tissue continuously releases IL-6, contributing to chronic inflammation.
7. Cytokine Release Syndrome
Seen after certain cancer treatments, particularly CAR-T cell therapy.
Symptoms of High IL-6 Levels
Symptoms vary widely depending on the underlying cause, but common findings include:
- Fever, chills, or night sweats
- Severe fatigue
- Joint or muscle pain
- Redness or swelling (autoimmune disease)
- Weight loss (cancers or chronic inflammation)
- Shortness of breath (severe infection or cytokine storm)
- Confusion, low blood pressure, or organ dysfunction (sepsis)
Extremely high IL-6 levels typically indicate a medical emergency.
Reference Ranges
Typical values may vary by laboratory, but commonly:
- Healthy individuals: < 5 pg/mL
- Mild inflammation: 5–30 pg/mL
- Moderate infection: 30–100 pg/mL
- Sepsis or cytokine storm: >100 pg/mL (may reach hundreds or thousands)
Doctors interpret IL-6 together with CRP, ferritin, procalcitonin, and clinical symptoms to determine severity.
Sample Type
- Blood sample (serum or plasma)
- No special tube required
Test Preparation
- Fasting is not required
- Inform your doctor about steroids or immunosuppressive medicines
- Mention chronic inflammatory or autoimmune conditions
- Stay hydrated for easier blood draw
When to Consult a Doctor
Seek medical attention if you experience:
- High or persistent fever
- Severe fatigue or body pain
- Difficulty breathing
- Red, swollen, or painful joints
- Symptoms of severe infection
- Confusion, low blood pressure, or rapid worsening of symptoms
- Known autoimmune disease with worsening flare
If IL-6 levels are high, doctors may order further testing, such as:
- CRP
- ESR
- CBC
- Ferritin
- Procalcitonin
- Liver and kidney tests
These help determine the cause and severity of inflammation.
Important Word Explanations
Cytokine: Small protein that helps immune cells communicate.
Pro-inflammatory: Increases inflammation to fight infection.
Acute-phase proteins: Substances produced by the liver during illness.
Sepsis: Life-threatening infection causing organ failure.
Cytokine storm: Severe immune overreaction damaging organs.
CRS: Cytokine release syndrome, often triggered by cancer therapies.
Hematopoiesis: Process of producing blood cells.
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