Type 2 cascade
Biomarker to interleukin
Click a cytokine. Fill bars use this patient's numbers: eosinophils report IL-5, FeNO reports IL-13, IgE reports IL-4. TSLP has no blood test — the case for it is a T2-low profile or failure of a downstream agent.
Allergen · virus · pollutant
IL-25 is a sister epithelial alarmin — no licensed antibody yet.
Bars = this patient's inferred cytokine tone
IL-5
Interleukin-5Th2 cells, ILC2, mast cells
The eosinophilopoietin. IL-5 is required for eosinophil differentiation in bone marrow, trafficking and tissue survival. Blocking IL-5 (mepolizumab, reslizumab, depemokimab) or IL-5Rα with ADCC (benralizumab) collapses the circulating eosinophil count.
Blood eosinophils 520 cells/µL indicate active IL-5-driven eosinophil survival.
Clinic biomarkers
- Blood eosinophilsSurrogate of IL-5 tone. GINA: use the highest count in the last 12 months, ideally off oral corticosteroid.≥150 qualifies most anti-IL-5; ≥300 stronger; ≥400 reslizumab
- Sputum eosinophilsDirect airway eosinophilia — closer to the IL-5 effect compartment than blood.≥2–3% confirms airway eosinophilia
Agents on this axis
On-therapy decoder
The same biomarker means different things on each drug. Do not re-stratify a switch on a suppressed-on-treatment count.
| Biomarker | Cytokine | Off treatment | Omalizumab | Anti-IL-5 | Dupilumab | Tezepelumab |
|---|---|---|---|---|---|---|
| Blood eosinophils | IL-5 | Disease activity. Use the 12-month peak, off OCS if possible. | Falls modestly. A rising count on omalizumab should prompt a search for EGPA or ABPA. | Falls predictably. Benralizumab depletes to ~0 — the count is then uninterpretable and is not a response metric. | Transient rise is expected (IL-4/13 blockade redistributes eosinophils). A symptomatic rise is not — watch for EGPA unmasking. | Falls. Neither FeNO nor eos should be used as a stopping rule. |
| FeNO | IL-13 | Epithelial T2 / IL-13 tone. Raised (≥25) even when eos are modest favours dupilumab. | Modest fall if the allergic pathway was driving iNOS. | Little change — FeNO is not an IL-5 reporter. Persistent high FeNO on anti-IL-5 is a reason to think about the IL-4/13 axis. | Falls, often sharply. Direction of travel only; do not stop the drug because FeNO has normalised. | Falls (upstream of IL-13). |
| Total IgE | IL-4 | Allergic burden and omalizumab dosing table. | Do not repeat. Omalizumab–IgE complexes cause a spurious rise. The baseline value sets the dose for the duration. | Unchanged. Anti-IL-5 does not touch class-switch. | Falls over months as IL-4-driven class-switch is silenced. | Modest fall. |
| Sputum eosinophils | IL-5 (+ IL-4/13) | Airway compartment. ≥3% confirms eosinophilic bronchitis. | Variable. | Suppresses. A return of sputum eos after a missed dose is an early relapse signal. | Usually falls with FeNO. | Falls. |