Dupilumab, a biologic used for severe eosinophilic asthma, targets which cytokine pathway, and what molecular mechanism underlies its efficacy?

• A Blockade of IgE via anti-IgE antibody, preventing mast cell and basophil degranulation
• B Blockade of the IL-4 receptor alpha subunit (IL-4Rα), inhibiting both IL-4 and IL-13 signaling simultaneously ✓
• C Inhibition of IL-5, blocking eosinophil differentiation and survival
• D Blockade of thymic stromal lymphopoietin (TSLP) receptor, preventing type 2 cytokine cascade initiation

Explanation

Dupilumab is a fully human monoclonal antibody targeting the IL-4 receptor alpha subunit (IL-4Rα), which is shared by both the type I IL-4 receptor (IL-4Rα/γc heterodimer) and the type II receptor (IL-4Rα/IL-13Rα1 heterodimer). This dual blockade simultaneously inhibits IL-4 signaling (driving Th2 differentiation and IgE class switching) and IL-13 signaling (driving mucus production, airway hyperreactivity, and fibrosis) — two central mediators of type 2 inflammatory asthma. Omalizumab blocks IgE (option A); mepolizumab/reslizumab block IL-5 (option C); tezepelumab blocks TSLP (option D).

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.