Eosinophils (%)

Eosinophils play a crucial role in the body's immune response. Understanding their function, levels, and how to optimize them is essential for maintaining overall health. 

Eosinophils are a type of white blood cell characterized by their distinctive granules that stain bright red with acidic dyes.

Eosinophils participate in immune responses against parasitic infections, allergic reactions, and asthma by releasing toxic proteins and enzymes that help destroy invading pathogens and modulate inflammation. Additionally, they contribute to tissue repair and regeneration after injury.

In this article, we will explore the definition and function of eosinophils.  We'll delve into labs for measuring eosinophil levels, how to interpret test results, related biomarkers, and natural ways to support and optimize eosinophil levels.

Understanding eosinophils and their role in the immune system can provide valuable insights into maintaining a healthy immune response and overall well-being.

Definition and Function of Eosinophils

What are Eosinophils?  [3., 7.]

Eosinophils are granulocytes derived from the same progenitor cells as monocytes-macrophages, neutrophils, and basophils; they are important components of the innate immune system.  

They are produced in the bone marrow, and their production is stimulated by cytokines like IL-5, IL-3, and GM-CSF, although IL-5 is particularly important in eosinophil production.  [3.] 

They constitute less than 5% of circulating leukocytes and can reside in tissues, particularly in the respiratory and gastrointestinal tracts, for up to 8 to 12 days. 

The function of eosinophils in the body includes defense against parasitic infections, modulation of immediate hypersensitivity reactions, and potential tissue repair. 

Eosinophils participate in Type 2 hypersensitivity, or allergic, responses.  Type 2 allergic responses involve the activation of Th2 cells, which stimulate the production of interleukins such as IL-4, IL-5, and IL-13, promoting IgE production and eosinophil recruitment. 

They contain granules with toxic proteins and enzymes, contribute to immune responses, and are regulated by T cells through the secretion of growth factors. 

Diurnal levels of eosinophils vary, typically peaking at night and decreasing in the morning, and can be influenced by various factors such as stress, medication use, and infections.

Eosinophil percentage is a measure of the proportion of eosinophils in the total white blood cell count, reflecting the percentage of eosinophils present in the blood.

Eosinophilia is a condition of excessive eosinophils; it is defined as an increase in circulating eosinophils exceeding 500 /mm^3.  It can be categorized as mild, moderate, or severe based on eosinophil counts. 

Function of Eosinophils: What Do Eosinophils Do in the Body?

Eosinophils are white blood cells involved in the innate immune response: they are classically thought to play a role in parasitic defense and allergic reactions.  However, emerging research demonstrates additional roles of eosinophils:  [3., 16.] 

Eosinophils, granulocytes derived from the same progenitor cells as monocytes-macrophages, neutrophils, and basophils, are components of the innate immune system.  They play crucial roles in defense against parasitic infections and intracellular bacteria.

Eosinophil granules contain toxic proteins like major basic protein and eosinophil cationic protein, effective against parasites and mammalian cells, and bind heparin neutralizing its anticoagulant activity.

They modulate immediate hypersensitivity reactions by degrading or inactivating mediators released by mast cells, such as histamine and leukotrienes.

They regulate immune functions through cytokine secretion, granule products, and direct cellular interactions, from innate to adaptive immunity, extending to non-immune cells.

Roles of Eosinophils in the Immune System:  [3., 16.] 

• Eosinophils participate in lymphocyte recruitment and homeostasis, affecting T-cell homing, B-cell proliferation, and antibody production.

• They act as antigen-presenting cells, promoting antigen-specific T-cell proliferation and driving Th2 polarization.

• Eosinophils interact with dendritic cells, regulating Th2 inflammation, and other immune responses.

• They play roles in recognizing pathogens through Toll-like receptors and release of anti-parasitic mediators contained within their granules, aiding in pathogen clearance.

• Eosinophils participate in innate recognition and regulation of non-adaptive immunity.

• They combat pathogens by releasing mitochondrial DNA and forming extracellular DNA traps.

• Eosinophils express a unique repertoire of pattern recognition receptors, including Toll-like receptors (TLRs).

• In viral infections, eosinophils recognize viral RNA through TLRs like TLR7 and contribute to antiviral defense mechanisms.

• However, they may exacerbate viral infections in some cases, such as human rhinovirus, by inhibiting epithelial interferon production.

• Eosinophils cooperate with other immune cells like macrophages to prevent the spread of viral infections, particularly in the lungs.

• Additionally, eosinophils regulate local cytokine milieu and glucose homeostasis in adipose tissue, influencing macrophage polarization and metabolism.

• Emerging research suggests that eosinophils may influence neuronal activity and homeostasis, potentially contributing to neurologic symptoms observed in allergic diseases.  [WEN>>>

Roles of Eosinophils in the Respiratory System:

• In allergic diseases like asthma, eosinophils release cytokines like IL-5 and GM-CSF, promoting airway hyperreactivity.

• Major eosinophil granule products, such as MBP and EPO, contribute to airway inflammation, smooth muscle contraction, and mast cell degranulation in asthma.

• Eosinophils also play roles in tissue remodeling and repair processes in asthma, contributing to lung fibrosis and epithelial damage.

• In allergic disorders, eosinophils and mast cells mutually potentiate each other's activation, leading to the release of allergic mediators and cytokines.

• Eosinophils orchestrate asthma and allergic diseases by promoting inflammation, airway hyperreactivity, tissue remodeling, and cross-talk with mast cells, contributing to disease progression and exacerbations.

Roles of Eosinophils in the Gastrointestinal System:  [16.] 

• In the gastrointestinal tract, eosinophils promote IgA production, enhance mucus secretion, and influence intestinal microbiota, maintaining gut homeostasis and immune function.

Roles of Eosinophils in Glucose Regulation:  [17., 18.]

The intricate interplay between the immune system and metabolic regulation significantly influences various chronic metabolic disorders like obesity, type 2 diabetes (T2D), and cardiovascular diseases. 

Chronic low-grade immune system activation, evidenced by markers such as white blood cell count and cytokines, contributes to T2D pathogenesis. Eosinophils, a type of white blood cell, are activated in allergic diseases and infections, and intriguingly, patients with asthma show a reduced risk of developing diabetes. 

Recent animal studies have suggested that eosinophils might actively participate in T2D pathogenesis. In a community-based study in China, researchers explored the association between peripheral eosinophil percentage and T2D, impaired glucose regulation, and insulin resistance. 

They observed that higher eosinophil percentages were associated with a reduced risk of T2D and impaired glucose regulation, along with lower insulin resistance in individuals with normal glucose tolerance.  [18.] 

Eosinophils may also unexpectedly play a crucial role in metabolic homeostasis by maintaining alternatively activated macrophages (AAMs) in adipose tissue. AAMs are essential for glucose homeostasis and are induced by the cytokines IL-4 and IL-13. 

Eosinophils are identified as the primary IL-4-expressing cells in white adipose tissues of mice. They migrate into adipose tissue through an integrin-dependent process and reconstitute AAMs via an IL-4/IL-13-dependent mechanism. Mice lacking eosinophils exhibit increased body fat, impaired glucose tolerance, and insulin resistance, especially when on a high-fat diet. 

Conversely, helminth-induced adipose eosinophilia improves glucose tolerance. These findings suggest a previously unrecognized role for eosinophils in metabolic homeostasis through the maintenance of adipose AAMs.  [17.] 

This finding suggests a potential protective role of eosinophils in glucose metabolism regulation. However, the exact mechanisms underlying this relationship remain to be fully elucidated, and further research is warranted to clarify the intricate connections between eosinophils and glucose regulation in metabolic disorders.

What Are Eosinophils % in Blood Tests?

In blood tests, the eosinophil percentage refers to the proportion of white blood cells that are eosinophils, typically reported as a percentage of the total white blood cell count. 

Normal eosinophil percentages typically range from 0 to 8%, although this can vary slightly depending on the laboratory's reference range. 

Elevated eosinophil percentages, known as eosinophilia, may indicate various conditions, including allergies, asthma, parasitic infections, autoimmune diseases, and certain types of cancers. 

Conversely, decreased eosinophil percentages may occur in response to corticosteroid medications, stress, or certain types of acute infections. 

Interpreting eosinophil percentages in conjunction with clinical symptoms and other laboratory findings is crucial for diagnosing and managing underlying health conditions.

Laboratory Testing for Eosinophils

General Testing Information, Preparation and Sample Type

Eosinophils are typically included as part of routine blood work called a complete blood count (CBC) with a differential, where the percentage of eosinophils is measured among other types of white blood cells. 

This test is usually conducted using a blood sample obtained via venipuncture, where a healthcare professional collects a small amount of blood from a vein, typically in the arm. The blood sample is then analyzed in a laboratory to determine the absolute count and percentage of eosinophils present in the bloodstream.

No special preparation is typically required for this test, although in certain situations the ordering healthcare provider may request discontinuing certain medications or supplements. 

Interpreting Eosinophil Test Results

Reference Range for Eosinophil %

It is important to consult reference ranges from the laboratory used.  However, a common eosinophil % for adults is 0%-8%.  [8.] 

In children ages 4-10, a common reference range is 2.4%-2.8%.  [5.] 

Clinical Significance of High Levels of Eosinophils

A high eosinophil count or % is called eosinophilia.  Eosinophilia is defined as a peripheral blood eosinophil count exceeding 500/mcL (> 0.5 × 10^9/L).  The typical eosinophil % in blood is 0-6%.  

Peripheral eosinophilia is characterized as  [7.]

Mild: 500 to 1500/mcL (0.5 to 1.5 × 109/L)

Moderate: 1500 to 5000/mcL (1.5 to 5 × 109/L)

Severe: > 5000/mcL (> 5 × 109/L)

Severe eosinophilia may potentially lead to organ damage, particularly if eosinophil levels persist above 1500/mcL (1.5 × 10^9/L). Organ damage typically results from tissue inflammation and reactions to cytokines and chemokines released by eosinophils, with manifestations affecting organs such as the heart, lungs, spleen, skin, and nervous system.

Eosinophilia can stem from diverse causes, commonly associated with allergic reactions, parasitic infections, or hematologic disorders. It can manifest as reactive (secondary) or primary hematologic disorder-related eosinophilia. 

Diagnosis involves targeted testing guided by clinical suspicion, with treatment directed towards addressing the underlying cause.

Eosinophilia may be asymptomatic, or it can present with various symptoms depending on the pathogenesis and organ systems involved.  Common symptoms in patients with primary eosinophilia include:  [2.]

• Fatigue
• Cough
• Shortness of breath
• Pain and/or swelling
• Rash
• Fever
• Retinal lesions
• Other symptoms may also be present depending on the etiology.  

Common causes of eosinophilia include: [7., 11.]

Helminthic parasites: infections such as Toxocariasis and Strongyloides stercoralis can trigger eosinophilia, often without significant symptoms but posing risks of disseminated infections.

Allergic and immunologically-mediated diseases: conditions like asthma, Churg-Strauss syndrome, and allergic bronchopulmonary aspergillosis can cause eosinophilia, especially when eosinophil counts exceed certain thresholds.

Adverse drug reactions: medications, including anticonvulsants and antibiotics, may induce eosinophilia, with manifestations varying from organ-specific reactions to systemic syndromes like drug reaction with eosinophilia and systemic symptoms (DRESS).

‍Neoplastic diseases: various cancers, such as Hodgkin's disease and T cell lymphoma, may trigger eosinophilia as a paraneoplastic phenomenon.

Rare immunodeficiency disorders: conditions like hyper-IgE syndrome and Omenn's syndrome can lead to eosinophilia due to underlying immune system dysregulation.

Organ-specific eosinophilic disorders: disorders such as eosinophilic pneumonia and eosinophilic gastroenteritis can be associated with blood eosinophilia, often presenting with specific symptoms related to affected organs.

Hypereosinophilic syndromes: these encompass a diverse group of disorders characterized by persistent eosinophilia, often with multi-organ involvement and potential for severe complications. Variants include myeloproliferative HES (M-HES) and lymphocytic HES (L-HES), each with distinct pathogenic mechanisms and clinical presentations.

The pathophysiology of eosinophilic esophagitis is not fully understood, but it is known that this is more common in atopic patients.  Eosinophils are not normally found in the esophagus.  

Known factors influencing eosinophilic esophagitis include:  [12.]

Immunogenic reaction to antigens: eosinophilic esophagitis (EoE) results from an immune response to various antigens commonly found in food and air, triggering inflammation in the esophageal mucosa.

Genetic factors: there is a strong genetic component involved in EoE's pathogenesis, with studies suggesting a high concordance among family members. The TSLP gene, located on the male X chromosome, is implicated in EoE, stimulating Th2 cells and inducing the release of proinflammatory cytokines like IL5, IL13, and IL15, which recruit eosinophils.

Environmental triggers: exposure to environmental antigens, food, or aeroallergens can initiate the immunogenic process leading to esophageal inflammation. Eotaxin-3, overexpressed in EoE patients, plays a crucial role in recruiting eosinophils to the esophageal mucosa.

Cytokine involvement: TGF-B, released by eosinophils and mast cells, contributes to esophageal remodeling and smooth muscle dysfunction, leading to various esophageal dysfunctions such as dysphagia, epigastric pain, and food impaction.

Gender and age: EoE is more common in men, particularly Caucasian and non-Hispanic white men, with a higher prevalence in the pediatric population among boys. The mean age of diagnosis is 34 years, with the condition most prevalent in men during their 20s and 30s.

Clinical Significance of Low Levels of Eosinophils

Low levels of eosinophils, also known as eosinopenia, tend to be an incidental finding on blood work, as low levels do not tend to cause problems by themselves.  Typically, a healthy immune system compensates for a lower level of eosinophils.  

Certain conditions can cause low eosinophils, and these do require medical intervention.  These include Cushing's Syndrome, corticosteroid use, and bacterial sepsis.  [14.]

Cushing’s Syndrome, Elevated Glucocorticoids, and Eosinophils  [9., 18.]

Cushing's syndrome arises from prolonged exposure of tissues to elevated levels of cortisol, resulting in a spectrum of symptoms including characteristic physical features, muscle weakness, depression, hypertension, osteoporosis, and hyperglycemia. Glucocorticoid excess, a hallmark of Cushing's syndrome, not only disrupts glucose metabolism but also modulates immune cell function, leading to compromised immunity and a higher susceptibility to infections.

Recent research has highlighted the role of immune cells, particularly eosinophils, in regulating systemic glucose metabolism. Eosinophils play a crucial role in maintaining glucose homeostasis by secreting Th2 cytokines, which modulate macrophage polarization and alleviate glucose intolerance. 

Interestingly, patients with Cushing's syndrome exhibit lower eosinophil counts compared to healthy individuals, suggesting a potential link between eosinopenia and glucose dysregulation in this population.

Moreover, Cushing's syndrome is characterized by a chronic low-grade inflammatory state, marked by alterations in leukocyte populations. While glucocorticoid excess induces leukocytosis and granulocytosis, it reduces the number of CD4+ T cells and increases CD8+ T cells, resulting in an imbalance in the immune profile. 

Importantly, the eosinophil count is inversely correlated with cortisol levels in patients with Cushing's syndrome, indicating a suppressive effect of glucocorticoids on eosinophil numbers.

Further analysis revealed associations between eosinophil counts and markers of glucose metabolism in patients with adrenal Cushing's syndrome. Lower eosinophil counts tended to correlate with higher levels of blood glucose and glycated hemoglobin, suggesting a potential role of eosinopenia in the development of glucose intoleance. 

Additionally, leukocyte counts showed an inverse relationship with eosinophil counts, underscoring the interplay between inflammation and eosinophil levels in Cushing's syndrome.  [9.]

‍Sepsis and Low Eosinophils  [1.] 

Septic shock, a significant contributor to global mortality, often leads to acute respiratory distress syndrome (ARDS) with a mortality rate exceeding 60%. Both conditions stem from dysregulated immune responses marked by severe inflammation. 

Eosinophils, typically associated with steroid responsiveness in airway diseases, exhibit low levels in sepsis and ARDS. This deficit may signify immune imbalance or result from eosinophil consumption, potentially exacerbating tissue damage and inflammation. 

Studies assessing eosinophil levels in sepsis patients reveal associations between persistent eosinopenia and increased mortality. In ARDS, bronchoalveolar lavage eosinophils are elevated in the late phase, correlating with disease severity. 

Peripheral eosinophil activity is also linked to survival in ARDS. However, the exact role of eosinophils in these conditions—whether they contribute to immune balance or exacerbate tissue injury—remains elusive. 

Further research is needed to elucidate eosinophils' mechanistic involvement and potential therapeutic implications in sepsis and ARDS.

Related Biomarkers

Eosinophils are one type of white blood cell.  It is important to assess white blood cells together to understand the balance of white blood cells present, and identify any excess, deficiencies, or imbalances.  This information is all included as part of the complete blood count  (CBC).  

Other biomarkers to consider may include IgE levels and inflammatory markers such as CRP and ESR  (erythrocyte sedimentation rate).

IgE Antibodies

Testing for IgE antibodies alongside eosinophil counts enhances the diagnostic accuracy for allergic conditions and asthma. Elevated IgE levels indicate sensitization to specific allergens, aiding in identifying triggers for allergic reactions. 

When combined with eosinophil counts, IgE testing provides a more comprehensive understanding of the immune response, guiding personalized management strategies for allergic diseases.

CRP

The combination of testing C-reactive protein (CRP) levels alongside eosinophil counts provides clinicians with a more comprehensive assessment of inflammatory processes. 

While eosinophils are indicative of type 2 inflammation and certain allergic conditions, CRP serves as a broader marker of overall inflammation, aiding in the diagnosis and monitoring of various infections, inflammatory diseases, and postoperative complications. 

Together, these biomarkers offer valuable insights into the inflammatory status of patients, guiding treatment decisions and assessing response to therapy.

‍ESR

The ESR blood test, or erythrocyte sedimentation rate test, is a simple blood test that measures the rate at which red blood cells settle to the bottom of a tube over a specified period. The test indirectly measures inflammation in the body, as inflammatory proteins in the blood cause red blood cells to stick together and fall more quickly than usual. 

The ESR test is nonspecific and can be influenced by various factors such as age, sex, anemia, and certain medications. It is often used as an initial screening tool to detect and monitor inflammatory conditions, infections, autoimmune diseases, and certain cancers, although further diagnostic tests are usually needed to confirm a specific diagnosis.

Natural Ways to Support Healthy Eosinophil Counts

A healthy balance of eosinophils requires a healthy, balanced immune system.  Natural strategies include those that support immune health and balance.  

A Healthy Diet: consume a balanced diet rich in fruits, vegetables, whole grains, and lean proteins, which may help regulate immune function and maintain healthy eosinophil levels.  [15.] 

Incorporate Anti-Inflammatory Foods: anti-inflammatory foods such as fatty fish (salmon, mackerel), nuts, seeds, and olive oil may help reduce inflammation and support immune balance.  [15.] 

Avoid Inflammatory Foods: minimize intake of processed foods, sugary snacks, and high-fat foods, which may contribute to inflammation and immune dysregulation.  [10.] 

Assess Vitamin D Levels and Supplement, if Necessary: low levels of vitamin D are inversely associated with eosinophil counts and linked to allergies, asthma and atopic conditions.  [13.] 

Prioritize sleep: ensure adequate sleep by maintaining a consistent sleep schedule and creating a relaxing bedtime routine, as sufficient sleep is crucial for immune system function.  [6.]

Seek Medical Support, if Necessary: if you are concerned about high eosinophil levels or experience symptoms such as unexplained fever, fatigue, or persistent infections, seek medical attention promptly for proper evaluation and management.

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