Unit Converter
Interleukin‐6 (IL‐6)
Synonyms
- IL-6
- Interleukin-6
- B-cell differentiation factor
- Cytokine IL-6
- Pro-inflammatory mediator
- Acute-phase cytokine
Units of Measurement
- pg/mL
- pg/dL
- pg/100 mL
- pg%
- pg/L
- ng/L
Key Conversions
1 pg/mL = 100 pg/dL = 100 pg% = 100 pg/100 mL
1 pg/mL = 1 ng/L
1 pg/dL = 0.01 pg/mL
1 pg/L = 0.001 pg/mL (rarely used clinically)
Description
Interleukin-6 (IL-6) is a pleiotropic cytokine produced by:
- Macrophages
- Monocytes
- T-cells & B-cells
- Endothelial cells
- Fibroblasts
- Adipose tissue
IL-6 plays a central role in:
- Acute inflammation
- Immune activation
- Cytokine storm
- Induction of CRP, fibrinogen and other acute-phase reactants
Acts via:
- Classical signaling (anti-inflammatory)
- Trans-signaling (pro-inflammatory)
- Soluble IL-6 receptor (sIL-6R) pathways
Physiological Role
1. Acute-Phase Response
Stimulates liver to produce:
- CRP
- Serum amyloid A
- Fibrinogen
- Ferritin
2. Immune Regulation
Impacts:
- B-cell maturation into plasma cells
- T-cell activation
- Fever generation (via hypothalamus)
3. Metabolic Effects
- Regulates glucose metabolism
- Released from adipose tissue in obesity
4. Hematopoiesis
Promotes production of neutrophils in bone marrow.
Clinical Significance
HIGH IL-6 (Most important clinically)
1. Sepsis & Septic Shock
- IL-6 rises early, often before CRP
- High IL-6 strongly correlates with mortality
- Used in ICU prognostic scoring
2. Cytokine Storm Syndromes
Seen in:
- Severe COVID-19
- HLH (Hemophagocytic Lymphohistiocytosis)
- CAR-T cell therapy toxicity
- MAS (Macrophage activation syndrome)
Typical levels: hundreds to thousands of pg/mL
3. Autoimmune & Rheumatologic Diseases
- Rheumatoid arthritis
- SLE
- Juvenile idiopathic arthritis
- Vasculitis
4. Infections
Viral, bacterial, or fungal infections produce elevated IL-6 before other markers rise.
5. Malignancy-Related Inflammation
- Multiple myeloma
- Lymphomas
- Solid tumors
IL-6 acts as a growth factor for some cancers.
6. Obesity & Metabolic Syndrome
Adipose tissue produces IL-6 → chronic low-grade inflammation.
7. Organ Failure
Elevated in:
- ARDS
- Acute pancreatitis
- Severe burns
LOW IL-6
Usually not clinically significant.
Seen in:
- Immunosuppression
- Corticosteroid use
- Early stages of mild infection
Reference Intervals
Healthy Adults
- < 7 pg/mL
Some labs use < 5 pg/mL
Mild Inflammation
- 7–50 pg/mL
Significant Inflammation / Infections
- 50–200 pg/mL
Severe Infection / Sepsis
- 200–1000+ pg/mL
Cytokine Storm
- >1000 pg/mL
- Severe COVID-19 & HLH: often >3000–5000 pg/mL
Diagnostic Uses
1. Sepsis Early Detection
- IL-6 rises before CRP, PCT
- Guides severity assessment
2. Cytokine Storm Monitoring
Used in:
- COVID-19 ARDS
- CAR-T cell induced CRS
- HLH / MAS
High IL-6 guides therapy (e.g., tocilizumab).
3. Autoimmune Disease Activity
Correlates with:
- RA disease activity
- SLE flares
- Systemic vasculitis
4. Prognosis in Critical Illness
Higher IL-6 = worse outcomes in:
- Sepsis
- Pancreatitis
- Trauma
- Burns
5. Oncology
IL-6 elevated in:
- Multiple myeloma (IL-6 is a myeloma cell growth factor)
- Solid tumor inflammation
6. Metabolic Diseases
Obesity → chronic IL-6 elevation
Linked to insulin resistance.
Analytical Notes
- Serum or plasma acceptable
- Hemolysis minimal impact
- Must be tested within hours or frozen (unstable at RT)
- Measured by ELISA or chemiluminescent immunoassays
- Diurnal variation: higher in early morning
- IL-6 rises rapidly, peak within 2–6 hours of infection onset
Clinical Pearls
- IL-6 rises much earlier than CRP or ferritin; excellent early inflammatory marker.
- Very high IL-6 (>1000 pg/mL) strongly suggests cytokine storm.
- IL-6 levels help assess response to anti-IL-6 therapy (tocilizumab).
- Obesity causes chronic mild elevation due to adipocyte secretion.
- IL-6 correlates with fever severity.
Interesting Fact
IL-6 is one of the primary cytokines responsible for the “flu-like” symptoms during infections: fever, malaise, muscle pain, and fatigue.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Cytokines.
- Mayo Clinic Laboratories - Interleukin-6.
- ARUP Consult - IL-6 in Inflammation & Cytokine Storm.
- ACCP/ATS Sepsis Guidelines.
- COVID-19 Cytokine Storm Consensus Papers.
- NIH - Interleukin-6 Biology.