Dupilumab is a biologic approved for severe atopic asthma and atopic dermatitis. Its mechanism addresses which cytokine signalling pathway?
- A Blocks the shared IL-4 receptor alpha (IL-4Ralpha) subunit, simultaneously inhibiting both IL-4 (type I receptor) and IL-13 (type II receptor) signalling — the key type 2 inflammation cytokines ✓
- B Blocks IL-5 receptor alpha on eosinophils, reducing eosinophil survival and maturation
- C Neutralises IgE, preventing mast cell and basophil degranulation in both early and late phases of asthma
- D Blocks TSLP (thymic stromal lymphopoietin), the epithelial-derived alarmin that initiates the type 2 inflammatory cascade
Explanation
Dupilumab is a fully human monoclonal antibody targeting the IL-4 receptor alpha (IL-4Ralpha) chain, which is a shared subunit of both the type I IL-4 receptor (IL-4Ralpha + gamma-c, expressed on T and B cells) and the type II receptor (IL-4Ralpha + IL-13Ralpha1, expressed on non-hematopoietic cells like epithelium). By blocking IL-4Ralpha, dupilumab simultaneously prevents both IL-4 and IL-13 signalling, attenuating IgE class switching, goblet cell hyperplasia, mucus hypersecretion, and airway hyperresponsiveness. Anti-IL-5 is mepolizumab/benralizumab; anti-IgE is omalizumab; anti-TSLP is tezepelumab.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.