Biomarkers of Immunity: Eosinophils

Optimal Takeaways

Eosinophils are a subset of white blood cells that play a primary role in allergies, asthma, and in the immune response to parasites. They also have a responsibility to maintain immune balance and homeostasis. Elevated levels are associated with type-II immune reactions such as allergies and asthma, parasitic infection, eosinophilic gastrointestinal disorders, autoimmune disease, some malignancies, and metabolic syndrome. Low levels are seen with corticosteroid therapy, Cushing’s disease, acute bacterial infection, and most viral infections.

Eosinophils, Absolute    

Standard Range: 0.00 – 0.50 k/cumm (0.00 – 0.50 giga/L)

The ODX Range: 0.03 – 0.2 k/cumm (0.03 – 0.2 giga/L)

Eosinophils %

Standard Range: 0.00 – 3.00%

The ODX Range: 0.00 – 3.00%

Low eosinophil counts are associated with eosinopenia, increased adrenosteroid production (Pagana 2021), Cushing syndrome, corticosteroid therapy (Deyrup 2022), recurrent C. difficile infection (Klion 2020), acute bacterial infection, most viral infections except for HIV (Ramirez 2018), cytokine storm associated with COVID-19 (Koc 2022).

High eosinophil counts are associated with eosinophilia, allergic reactions, autoimmune disease, parasitic infections, eczema, leukemia (Pagana 2021), asthma, connective tissue disorders, myeloproliferative disorders, certain lymphomas (Deyrup 2022), HIV (Klion 2020), chronic inflammation (Tigner 2021), and intestinal worms (Justiz Vaillant 2022).

Elevated eosinophils are also associated with metabolic syndrome (Babio 2013, Kim 2008), chronic rhinosinusitis with nasal polyps, progressively worsening asthma, hypereosinophilic syndromes, and eosinophilic gastrointestinal disorders, including eosinophilic esophagitis, gastroenteritis, and colitis (Wechsler 2021).

Overview

Eosinophils are granulocyte white blood cells capable of directly killing pathogenic protozoa and worms through reactive oxygen radicals and nitric oxide (Justiz Vaillant 2022). Eosinophils can also ingest or “phagocytize” antigen-antibody complexes as part of an allergic response. Once the response has diminished, the level of eosinophils involved should decrease (Pagana 2021). Eosinophils can play a homeostatic role and modulate inflammation associated with an immune response by releasing arylsulfatase and histaminase enzymes to break down vasoactive leukotrienes and histamine, respectively (Tigner 2021). However, toxic compounds released from eosinophils can also damage host tissues and disrupt homeostasis (Ramirez 2018).

Other potential homeostatic roles for eosinophils include metabolism, glucose homeostasis, fat deposition, epithelial and microbiome regulation, liver and muscle repair, neuronal regulation, and tissue remodeling and development. However, more research is needed in humans to confirm these associations. The optimal range for absolute eosinophils is 0.03 – 0.3 k/cumm in a healthy adult, while a level above 0.4 k/cumm, or above 3%, is considered pathological. Higher absolute eosinophil counts were associated with better survival in metastatic melanoma and Hodgkin lymphoma patients (Wechsler 2021).

The physiological function of eosinophils extends beyond their anti-parasitic role and involvement in type-II immune responses, e.g., asthma, allergies, eosinophilic esophagitis, and inflammatory bowel disease (IBD). Eosinophils’ production and release of chemokines, cytokines, lipid mediators, peroxidase, and other bioactive substances affect many processes throughout the body. Eosinophils are also found under homeostatic conditions, perhaps in a “surveillance” role, in mucosal tissues (e.g., intestines, lungs, uterus, and mammary glands), adipose tissue, and the thymus gland. Resident eosinophils in the intestine make up 5-35% of all white blood cells throughout the body (Shah 2020).

Eosinophilia occurs at an absolute eosinophil level above 0.45 k/cumm, while a level of 1.5 k/cumm and above is considered hypereosinophilia, a condition associated with organ damage and progression to hypereosinophilic syndrome. Known causes of hypereosinophilia include parasitic infection, inflammatory disorders, and lymphoid malignancies (Ramirez 2018). Eosinophilia can also be seen with HIV, an exception to the more common finding of low circulating eosinophils (eosinopenia) in viral infection. Eosinopenia is also observed with acute bacterial infection, where eosinophil levels maintain an inverse association with the bacterial load. Researchers note that eosinophil levels in the blood may be low. In contrast, levels in tissue can be elevated, possibly accounting for the previous incorrect assumption that eosinophils do not respond to bacterial or viral infections (Klion 2020).

An elevation in WBCs, including eosinophils, is observed with metabolic syndrome. Data from 4,377 participants in the PREDIMED study found that 63.6% had metabolic syndrome at baseline. The risk of having metabolic syndrome increased significantly with a mean absolute eosinophil count of 0.21 k/cumm compared to a lower mean value of 0.12 k/cumm. In the study, elevations in all subsets of white blood cells were associated with metabolic syndrome except for basophils (Babio 2013).

Earlier research had also revealed an association between eosinophils and metabolic syndrome based on the annual medical checkup records of 15,654 subjects. Individuals with the highest eosinophil counts of 0.177-2.67 k/cumm had a significantly higher risk of having metabolic syndrome than those with the lowest eosinophil level of 0.088 k/cumm (Kim 2008).

References

Babio, Nancy et al. “White blood cell counts as risk markers of developing metabolic syndrome and its components in the PREDIMED study.” PloS one vol. 8,3 (2013): e58354. doi:10.1371/journal.pone.0058354

Deyrup, Andrea T et al. “Essential laboratory tests for medical education.” Academic pathology vol. 9,1 100046. 13 Sep. 2022, doi:10.1016/j.acpath.2022.100046

Justiz Vaillant, Angel A., et al. “Physiology, Immune Response.” StatPearls, StatPearls Publishing, 26 September 2022.

Kim, Dong-Jun et al. “The associations of total and differential white blood cell counts with obesity, hypertension, dyslipidemia and glucose intolerance in a Korean population.” Journal of Korean medical science vol. 23,2 (2008): 193-8. doi:10.3346/jkms.2008.23.2.193

Klion, Amy D et al. “Contributions of Eosinophils to Human Health and Disease.” Annual review of pathology vol. 15 (2020): 179-209. doi:10.1146/annurev-pathmechdis-012419-032756

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Koc, Ibrahim, and Sevda Unalli Ozmen. “Eosinophil Levels, Neutrophil-Lymphocyte Ratio, and Platelet-Lymphocyte Ratio in the Cytokine Storm Period of Patients with COVID-19.” International journal of clinical practice vol. 2022 7450739. 3 Aug. 2022, doi:10.1155/2022/7450739

Ramirez, Giuseppe A et al. “Eosinophils from Physiology to Disease: A Comprehensive Review.” BioMed research international vol. 2018 9095275. 28 Jan. 2018, doi:10.1155/2018/9095275

Shah, Kathleen et al. “The emerging roles of eosinophils in mucosal homeostasis.” Mucosal immunology vol. 13,4 (2020): 574-583. doi:10.1038/s41385-020-0281-y

Tigner, Alyssa, et al. “Histology, White Blood Cell.” StatPearls, StatPearls Publishing, 19 November 2021.

Wechsler, Michael E et al. “Eosinophils in Health and Disease: A State-of-the-Art Review.” Mayo Clinic proceedings vol. 96,10 (2021): 2694-2707. doi:10.1016/j.mayocp.2021.04.025