Interleukin-5 (IL-5) is a cytokine, a signaling protein in the immune system. These molecules facilitate communication between immune cells, orchestrating responses to various threats. IL-5 is primarily produced by T helper 2 (Th2) cells, a subset of white blood cells, and plays a role in directing certain immune activities.
Key Roles in Immune Response
IL-5’s most recognized function revolves around eosinophils, a type of white blood cell. It stimulates the production, maturation, and activation of eosinophils in the bone marrow. IL-5 helps these cells migrate from the bone marrow to tissues and extends their lifespan by preventing programmed cell death.
IL-5-driven eosinophil activity and numbers are noticeable in allergic reactions. In these responses, eosinophils contribute to the inflammatory processes that lead to symptoms. IL-5 also aids in defense against parasitic infections, particularly helminths (worm-like parasites). Eosinophils are a significant component of the immune response to these invaders.
IL-5 also influences other immune cells and processes. It acts as a growth factor for B cells, especially B-1 cells, and induces B cells to produce immunoglobulin A (IgA) antibodies, important for mucosal immunity. It can also enhance histamine release from basophils, another white blood cell involved in allergic responses.
IL-5’s Involvement in Disease
Excessive IL-5 activity contributes to several inflammatory conditions. In severe eosinophilic asthma, elevated IL-5 levels drive the accumulation and activation of eosinophils in the airways. These activated eosinophils release toxic proteins and inflammatory mediators, leading to inflammation, airway narrowing, and tissue damage characteristic of asthma. This excessive eosinophil presence can result in increased mucus production and airway remodeling.
Beyond asthma, IL-5 and eosinophils are implicated in other allergic and inflammatory diseases. Allergic rhinitis (hay fever) and atopic dermatitis (eczema) also involve elevated IL-5 levels, contributing to tissue inflammation. Hypereosinophilic syndrome (HES) is a rare group of disorders characterized by persistently high levels of eosinophils in the blood and tissues, which can cause damage to various organs like the skin, heart, and lungs.
Continuous IL-5 stimulation leads to eosinophil degranulation, releasing substances like eosinophil peroxidase and major basic protein. These mediators directly contribute to inflammation, tissue injury, and the associated symptoms of these diseases. IL-5 can also make eosinophils more responsive to other stimuli, intensifying the inflammatory response.
Targeting IL-5 for Treatment
Understanding IL-5’s role in driving eosinophil-mediated inflammation has led to targeted therapies. These treatments aim to reduce eosinophil numbers and activity, alleviating symptoms and preventing tissue damage in diseases where IL-5 is overactive. A primary approach involves monoclonal antibodies that interfere with the IL-5 pathway.
Mepolizumab and reslizumab are antibodies that bind directly to IL-5. By binding to circulating IL-5, these medications prevent it from interacting with its receptor on eosinophils, inhibiting their activation, growth, and survival. This action effectively reduces the number of eosinophils in the blood and tissues.
Another strategy uses benralizumab, which targets the alpha subunit of the IL-5 receptor (IL-5Rα) on eosinophil surfaces. By blocking this receptor, benralizumab prevents IL-5 from binding and activating the eosinophil. Benralizumab also has a unique mechanism: its structure allows natural killer cells to bind to eosinophils and trigger their programmed cell death, leading to a more profound depletion. These anti-IL-5 therapies are primarily used for treating severe eosinophilic asthma and have shown promise in other eosinophil-driven conditions like hypereosinophilic syndrome and chronic rhinosinusitis with nasal polyps.