IL-5

Class

anti-IL-5 monoclonal antibody — mepolizumab

Pathway

prevents IL-5 binding to IL-5Rα on eosinophils, reducing eosinophil maturation/survival

Interleukin-5 (IL-5) is a signaling protein, or cytokine, produced chiefly by type 2 helper T cells and innate lymphoid cells. Its principal biological role is to direct the bone marrow to produce eosinophils, a type of white blood cell, and to support their survival and activation once released into tissue. Eosinophils are useful for defense against parasitic infections, but in many chronic inflammatory diseases they accumulate excessively in the airways, sinuses, skin, or blood vessels and contribute to tissue damage and symptoms. Monoclonal antibodies directed against IL-5 work by binding the free cytokine in circulation, preventing it from engaging its receptor (IL-5 receptor alpha) on eosinophil precursors and mature eosinophils. With this signal removed, fewer eosinophils are generated in the marrow and existing ones survive for a shorter time, lowering their numbers in blood and tissue. This approach is relevant to diseases where eosinophils are a primary driver of pathology, including certain forms of asthma characterized by eosinophilic airway inflammation, chronic rhinosinusitis with nasal polyps, hypereosinophilic syndromes, and eosinophilic granulomatosis with polyangiitis. Rather than broadly suppressing the immune system, this mechanism narrows its effect to a single cytokine axis governing one cell lineage.