Eosinophilic or ‘EOS’ inflammation can mediate organ dysfunction in eosinophil-driven diseases through interactions with structural tissue cells and other immune cells.1–4 Learn more about how eosinophils can drive disease pathology in this educational module.
Eosinophils, which develop in the bone marrow, are differentiated effector cells that are primarily tissue-dwelling.2,5,6 Increases in recruitment to tissue, differentiation, activation, and survival of eosinophils can occur under the influence of cytokines such as IL-3, IL-5, and GM-CSF.4,5,11,12 The functional diversity of eosinophils is enabled by a repertoire of cell surface receptors, including receptors for cytokines, adhesion molecules, and complement components.4,12,13 This receptor architecture supports efficient recruitment to sites of inflammation, promotes the release of further inflammatory mediators, and can amplify activation in response to local cytokine release.4,12,13
Upon activation, eosinophils release a mixture of granules (eg EPX, MBP, ECP, and EDN) that can drive tissue dysfunction and initiate downstream inflammatory signaling.12 They also generate EETs and CLCs, which can further propagate tissue damage and sustain local immune cell activation.2
Although eosinophils are present in the tissues of healthy humans, their precise physiological role remains incompletely understood.2,3 Much of what is known about eosinophil biology comes from research using in vitro models and animal studies, which provide valuable insights but do not fully clarify their roles in humans.3
Proposed roles for eosinophils span both immune and non-immune domains.14,15 Within the immune system, it has been shown that eosinophils can contribute to innate and adaptive immunity, acting as early responders to environmental stimuli while also influencing the behavior of other immune cells.14,15 Beyond immunity, eosinophils have also been proposed to play a role in reproductive homeostasis.14 Additional hypotheses point toward contributions to mammary gland development, as well as the maintenance of gastrointestinal homeostasis, where eosinophils are consistently present in the healthy gut.14
Importantly, long-term eosinophil depletion studies in humans have not been associated with significant physiological abnormalities, increased susceptibility to infection, or heightened malignancy risk.3,16 This observation has led to the hypothesis that humans possess sufficient immune redundancy, including alternative pathways and cell types capable of compensating for eosinophil loss, thereby preventing noticeable negative clinical consequences when eosinophils are depleted.3
Eosinophilic inflammation in tissues is now recognized as a key contributor to the pathophysiology of several diseases, including SEA, EGPA, and HES.2,4,5,16,17
In these conditions, eosinophils become drivers of chronic inflammation, which can lead to organ dysfunction.2,4 The specific consequences vary by disease, but can include:
Certain eosinophil-driven diseases are associated with elevated mortality rates.31–33 This is particularly evident in systemic diseases, such as EGPA and HES, where uncontrolled eosinophilic inflammation may result in life-threatening complications, including cardiomyopathy or vasculitis.33–35
Owing to their central role in progression of these eosinophil-driven diseases, targeting eosinophils to reduce inflammation has become an established disease management strategy.7,8
Learn more about the role of eosinophils in SEA, EGPA, and HES in the dedicated educational modules
When eosinophil progenitors in the bone marrow mature, they are released into the circulation and migrate to sites of inflammation, such as the airway tissue.13,36
Eosinophils are key effector cells within the inflammatory cascade and can contribute to tissue damage through a complex network of cellular interactions and cytokine signaling.13,36–41 Increases in recruitment to tissue, differentiation, activation, and survival of eosinophils can occur under the influence of several cytokines, including IL-3, IL-5, and GM-CSF.4,5,11
Once present in the affected tissue, eosinophils can play an important role as pathogenic cells and contribute to:
Through these interconnected pathways, eosinophils can become key drivers of tissue damage and dysfunction in disease.13,36–39,41 Eosinophil levels have been found to be raised across a heterogenous range of eosinophil-associated diseases, including SEA, EGPA, HES, IBD, atopic dermatitis, and CRSwNP.1,42–44
Release of eosinophil-derived proteins such as EPX, MBP, and ECP have been shown to directly injure the epithelium.1 These toxic mediators, along with release of ROS via EETosis, can result in compromised epithelial barrier integrity and persistent release of inflammatory mediators in diseases such as SEA, EGPA, and HES.1
Chronic eosinophilic inflammation can promote structural changes.1 The release of cytokines IL-13 and IL-4, as well as MBP, by eosinophils can drive fibroblast proliferation and extracellular matrix deposition via TGF-β, IL-6, IL-11, IL-13, and matrix metalloproteinases (eg MMP9). This can result in long-term tissue remodeling and even fibrosis in SEA, HES, and EGPA.1,18,44 The resulting clinical consequences of eosinophil-associated remodeling and eosinophil-driven fibrosis are often severe, with lasting impacts on patient quality of life, such as endomyocardial fibrosis and heart failure in HES, and airway remodeling and irreversible airway obstruction in SEA.18
Activated eosinophils can undergo EETosis, resulting in the release of granule proteins, CLCs, as well as EVs and ETs.1,21,45 These structures have been shown to increase the viscosity of mucus and promote plugging, which can cause airflow obstruction.1,21,45 Furthermore, release of leukotrienes and cytokines, such as IL-13, can promote mucus hypersecretion.1 Together, these mechanisms perpetuate type 2 inflammation and increase the probability of mucus plugging in asthma.18,21,45 Importantly, mucus within the airways is increasingly being recognized as a critical driver of disease symptoms through obstruction of the airway lumen and exacerbations.21,46,47
MBP, EPX, leukotrienes, and cytokines such as IL-13, released from eosinophils, are known to contribute to airway hyperresponsiveness.1 The release of mediators such as MBP and EPX has been shown to damage lung structural cells and promote airway hyperreactivity, which manifests as hallmark features of asthma such as bronchospasm, wheezing/coughing, airflow limitation, and dyspnea.1,43
Eosinophils can impact neural signaling via the release of mediators such as EDN, ECP, substance P, VIP, and NGF.1,42 In certain diseases, eosinophils can accumulate in close proximity to neural fibers and ganglia and have been hypothesized to exert both neuroinflammatory and neurotoxic effects.1,42
Management of eosinophil-driven diseases such as SEA, EGPA, and HES has historically relied on the use of corticosteroids, both local and systemic, to reduce the effects of inflammation.9 This is reflected in their inclusion in international guidelines for disease management and treatment.9,48–50
While both OCS and ICS can impact the inflammatory cascade, ICS are likely to act on the epithelium, reducing eosinophil recruitment, while OCS are likely to deplete the reservoir of circulating eosinophils.51
It is now widely recognized that corticosteroids are associated with adverse effects and corticoresistance, and that poor disease control is often reported despite their use.9 Reporting of adverse events is particularly associated with the use of systemic corticosteroids at high dose, for repeated cycles, or for a prolonged period of time.9
Some researchers suggest that eosinophils play a central role not only in driving inflammation but also in predicting disease course.4,10,52–54 These cells are considered a potential prognostic marker in several eosinophil-driven diseases, and have been explored for their ability to support a predict and prevent approach to disease management.4,10,52–54
CLC, Charcot-Leyden crystal; CRSwNP, chronic rhinosinusitis with nasal polyps; ECP, eosinophil cationic protein; EDN, eosinophil-derived neurotoxin; EET, extracellular eosinophilic trap; EETosis, eosinophil extracellular trap cell death; EGPA, eosinophilic granulomatosis with polyangiitis; EOS, eosinophil; EPX, eosinophil peroxidase; ET, eosinophilic trap; EV, extracellular vesicle; GM-CSF, granulocyte-macrophage colony-stimulating factor; HES, hypereosinophilic syndrome; IBD, inflammatory bowel disease; ICS, inhaled corticosteroid(s); IL, interleukin; MBP, major basic protein; MMP, matrix metalloproteinase; NGF, nerve growth factor; OCS, oral corticosteroid(s); ROS, reactive oxygen species; SEA, severe eosinophilic asthma; TGF-β, transforming growth factor beta; VIP, vasoactive intestinal peptide
EOSInflammation.com has been
developed by AstraZeneca.
For healthcare professionals only.
© 2026 AstraZeneca
Veeva ID: Z4-82630
Date of preparation: June 2026
