Eosinophils are a type of white blood cell, or leukocyte, that plays a dual role in the immune system. They are a standard part of the body’s defense against certain pathogens, but they are also central to the development and severity of allergic diseases. The actions of these cells are directly responsible for the characteristic inflammation and tissue damage seen in hypersensitivity reactions.
The Nature of Eosinophils
Eosinophils originate in the bone marrow, developing from hematopoietic stem cells under the influence of growth factors, notably Interleukin-5 (IL-5). They circulate briefly in the blood before migrating into tissues, where they primarily reside in the gastrointestinal tract, lungs, and skin. Structurally, they are identifiable by a bi-lobed nucleus and large cytoplasmic granules that stain brightly red with the dye eosin, giving the cells their name.
The primary function of the eosinophil is defense against multicellular parasites, such as helminths. To destroy these invaders, the granules contain a potent arsenal of pre-formed toxic proteins and enzymes. This powerful chemical payload is highly effective against large pathogens, but it also causes damage to the host’s own tissues when eosinophils are inappropriately activated during an allergic reaction.
Eosinophils’ Role in Acute Allergic Response
Eosinophil involvement in an acute allergic reaction, known as Type I hypersensitivity, begins shortly after allergen exposure. Mast cells and basophils, the first responders, release chemical signals that recruit eosinophils to the site of inflammation. This cellular movement, called chemotaxis, is driven by chemokines like eotaxin (CCL11), which bind to receptors on the eosinophil surface.
Once recruited, eosinophils become primed for activation by cytokines, such as Interleukin-5, which prolongs their survival and enhances responsiveness. These primed cells are triggered by allergen-specific Immunoglobulin E (IgE) antibodies bound to their surface receptors. When the allergen cross-links these IgE molecules, it signals the cell to undergo a rapid release of its granule contents, a process called degranulation.
The immediate impact of degranulation is the release of highly cytotoxic proteins, including Major Basic Protein (MBP) and Eosinophil Cationic Protein (ECP). These proteins are directly toxic to epithelial and nerve cells, contributing to tissue injury and irritation. Eosinophils also synthesize and release lipid mediators, such as leukotrienes, which are potent inducers of smooth muscle contraction. The release of these mediators contributes directly to immediate acute symptoms, causing effects like bronchoconstriction, increased vascular permeability, and tissue swelling. Furthermore, the Major Basic Protein can cause neighboring mast cells to degranulate, creating an amplifying cascade that sustains the acute response.
Chronic Eosinophilic Inflammation and Disease
When the allergic response becomes sustained or poorly regulated, the continued presence of eosinophils shifts the pathology from transient acute symptoms to chronic disease states. In these conditions, the continuous release of cytotoxic granule proteins causes significant and lasting damage to tissues. This prolonged chemical exposure leads to tissue remodeling, where normal tissue structure is permanently altered by fibrosis and excessive mucus production.
In the lungs, this chronic activity is the hallmark of eosinophilic asthma, a severe subtype of the disease. Eosinophils accumulate in the airways and release growth factors like Transforming Growth Factor-beta (TGF-β), which promotes the thickening of the airway walls. This remodeling permanently narrows the airways, resulting in persistent breathing difficulties and a reduced response to standard asthma treatments.
Another example is Eosinophilic Esophagitis (EoE), where the esophagus becomes infiltrated with high numbers of eosinophils. The resulting inflammation and tissue remodeling lead to the formation of rings and strictures, causing difficulty and pain when swallowing. A more systemic condition is Hypereosinophilic Syndrome (HES), defined by an absolute eosinophil count exceeding 1,500 cells per microliter for an extended period. The sustained high levels of eosinophils in the blood and tissue can damage organs like the heart, nervous system, and skin, leading to potentially life-threatening organ failure.
Clinical Management of Eosinophil Activity
The clinical assessment of eosinophil activity begins with a Complete Blood Count with Differential. This test determines the Absolute Eosinophil Count (AEC), which is the total number of cells per volume of blood. A count exceeding 500 cells per microliter is defined as eosinophilia, indicating an elevated level of these cells.
Initial management of elevated eosinophil counts involves the use of corticosteroids, which are broad anti-inflammatory medications that suppress the immune response and reduce eosinophil numbers. Since the long-term use of systemic steroids carries significant side effects, more targeted therapies have been developed. Newer, highly specific treatments focus on Interleukin-5 (IL-5), the cytokine that controls eosinophil maturation, survival, and activation.
These targeted medications are biologics, a class of drugs that includes monoclonal antibodies such as mepolizumab, reslizumab, and benralizumab. Mepolizumab and reslizumab bind directly to IL-5, preventing it from interacting with its receptor on the eosinophil surface. Benralizumab binds to the IL-5 receptor itself, triggering the destruction of the eosinophils through antibody-dependent cell-mediated cytotoxicity. These agents significantly reduce both blood and tissue eosinophil counts, controlling inflammation and preventing the tissue damage associated with chronic eosinophilic diseases.