Cytokines are signaling proteins that act as chemical messengers, coordinating the behavior of immune cells to mount an effective defense against pathogens. Interleukin-5 (IL-5) is a specific cytokine that plays a large role in type 2 immune responses, primarily associated with defending against parasites and mediating allergic reactions. Understanding the precise actions of IL-5 is important for grasping the mechanisms behind several common inflammatory diseases.
What is Interleukin-5 and Where is it Produced?
Interleukin-5 is classified as a homodimeric glycoprotein, meaning it is a protein with attached sugars that functions as a pair of identical subunits bound together. The gene encoding IL-5 is located on human chromosome 5, often near genes for other related signaling molecules.
The production of IL-5 is primarily the responsibility of T helper 2 (Th2) lymphocytes, a specialized subset of T cells that orchestrate the type 2 immune response. When the immune system encounters allergens or parasitic worms, activated Th2 cells begin secreting IL-5. Mast cells and eosinophils also contribute to IL-5 production, helping to amplify the local inflammatory signal.
The Central Role in Eosinophil Activity
The most significant function of Interleukin-5 is its comprehensive control over the life cycle of eosinophils, a type of white blood cell characterized by granules containing toxic proteins. IL-5 acts as the principal factor governing the differentiation, proliferation, activation, and survival of these cells. Eosinophils express a specific receptor on their surface which binds to IL-5.
In the bone marrow, IL-5 drives the maturation of eosinophil precursor cells, stimulating their division and development into mature eosinophils. It also orchestrates the mobilization of these cells from the bone marrow into the bloodstream and peripheral tissues. Once in the tissue, IL-5 prolongs the lifespan of the eosinophil by inhibiting programmed cell death, or apoptosis. This action ensures a sustained population of active eosinophils to combat persistent threats, such as helminthic infections.
Impact on Antibody Production
Beyond its primary effects on eosinophils, Interleukin-5 also influences B lymphocytes, the immune cells responsible for producing antibodies. IL-5 acts as a co-stimulator, aiding in the growth and differentiation of activated B cells into plasma cells. This function is particularly relevant in mucosal immunity and allergic responses.
Specifically, IL-5 significantly augments the production of Immunoglobulin A (IgA) and Immunoglobulin E (IgE) antibodies. For IgA, which is abundant in mucosal linings like the gut and airways, IL-5 acts mainly as a differentiation factor, promoting IgA-secreting plasma cells. In allergic responses, IL-5 works with other cytokines, such as Interleukin-4, to enhance the production of IgE, the antibody class associated with immediate hypersensitivity reactions.
Connection to Allergic and Inflammatory Diseases
The regulatory effects of IL-5 on eosinophils and antibody production link it directly to several inflammatory and allergic disorders. Conditions such as severe eosinophilic asthma, allergic rhinitis, and parasitic worm infections are characterized by high levels of IL-5 and an overabundance of eosinophils, known as hypereosinophilia. Excessive activation of eosinophils leads to the release of toxic granule contents, causing tissue damage, inflammation, and associated symptoms.
Targeting the IL-5 pathway has become a cornerstone of modern treatment for specific eosinophil-driven diseases. Therapeutic monoclonal antibodies have provided a way to neutralize the cytokine’s effect. Some biologics, such as mepolizumab and reslizumab, bind directly to IL-5, preventing it from attaching to the eosinophil receptor. Other drugs, like benralizumab, block the IL-5 receptor itself, leading to the destruction of the eosinophil. These targeted treatments effectively reduce the number and activity of eosinophils, offering relief for patients with severe inflammatory conditions.