Biomarkers of Immunity: Neutrophils

Optimal Takeaways

Neutrophils are the most abundant white blood cells in circulation and serve as the first line of defense against pathogens. They produce potent compounds that fight microorganisms and are able to engulf and digest bacteria directly through phagocytosis.

Neutrophils appear early in the process of inflammation, and elevated levels are seen with infection, cardiovascular disease, and metabolic syndrome. They are also increased in trauma or emotional distress as well. Low levels may be seen with bone marrow failure, radiation exposure, viral infections, and immune suppression.

Neutrophils, Absolute

Standard Range: 1.50 – 7.8 k/cumm (1.50 – 7.80 giga/L)

The ODX Range: 1.90 – 4.20 k/cumm (1.90 – 4.20 giga/L)

Neutrophils, %

Standard Range: 38.00 – 74.00%

The ODX Range: 50.00 – 60.00 %

Low neutrophils are associated with decreased production or increased destruction, which can be caused by radiation, bone marrow failure, autoimmune disease, and neutrophil extracellular traps (NETs) (Deyrup 2022). Low neutrophil counts are also associated with malnutrition, viral infections, overwhelming bacterial infection, aplastic anemia, Addison disease, and myelotoxic drugs e.g., chemotherapy (Pagana 2021).

High neutrophils are associated with acute infection (especially fungal or bacterial), corticosteroid therapy, chronic myeloid neoplasms, tissue necrosis (Deyrup 2022), myocardial infarction, and death in high-risk individuals (Horne 2005).

Elevated neutrophils are also associated with destabilization of atherosclerotic plaque; poorer outcomes in acute coronary syndromes, myocardial infarction, cardiac revascularization, and CABG surgery (Guasti 2011); oxidative tissue and organ damage; increased all-cause mortality (Leng 2005); physical or emotional stress; trauma; Cushing syndrome; inflammatory disorders including rheumatoid arthritis and thyroiditis, metabolic disorders including ketoacidosis, gout (Pagana 2021), and metabolic syndrome (Kim 2008, Babio 2013). 

Overview

Neutrophils are granulocytes that serve as the first line of immune defense. They are the most abundant WBC in circulation, although their lifespan can be as short as six hours. The primary function of neutrophils is the trapping, killing, and digesting of bacteria in a process called phagocytosis. Neutrophil production is stimulated by acute bacterial infection, trauma, and even emotional stress. Significant stimulation can result in the release of immature neutrophils called band cells, creating a “shift to the left” in WBC production, suggesting an ongoing acute or worsening infection (Pagana 2021).

Neutrophils release potent compounds, including reactive oxygen species, myeloperoxidase, lysosome, and cytokines. Neutrophil counts increase early in acute inflammation but may eventually be replaced by macrophages and lymphocytes. indicating more chronic inflammation (Pahwa 2022). Neutrophils are stimulated by cytokines and IgE antibodies, and they participate in hypersensitivity immune reactions, i.e., allergies (Justiz 2022).

The risk of all-cause mortality increased significantly as the neutrophil count rose above 4.43 k/cumm in a study of 624 community-dwelling women 65-101 years of age. Researchers note that neutrophils cause oxidative damage to many tissues and organ systems. Increased mortality was also associated with a total WBC count above 7.0 k/cumm or below 5.6 k/cumm, and a lymphocyte count below 1.54 k/cumm (Leng 2005).

Neutrophil-associated oxidative damage is a likely contributor to atherosclerosis and ischemic cardiovascular disease. A neutrophil count above 6.6 k/cumm was an independent predictor of myocardial infarction and death in high-risk individuals in a study of 3,227 undergoing coronary artery disease assessment (Horne 2005).

Low-grade inflammation is associated with metabolic syndrome, and research suggests that WBC elevations, including neutrophils, may help identify those at highest risk. A cross-sectional study of 15,654 subjects found that the risk of metabolic syndrome was significantly higher with a neutrophil count in the second and third tertiles of 2.80-3.67 and 3.67-8.19 k/cumm, respectively. The lowest risk was seen with a neutrophil count of 1.07-2.80 k/cumm (Kim 2008).

Elevated neutrophils were associated with an increased risk of metabolic syndrome in a review of data from 4,377 individuals as well. The risk of metabolic syndrome was greatest for those in the highest versus the lowest quartile for the neutrophil count, i.e., 4.43-5.90 k/cumm versus 2.2-2.89 k/cumm (Babio 2013).

The absolute neutrophil count indicates the total number of cells in circulation, while %neutrophils indicate the percentage of white blood cells made up of neutrophils.

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

Guasti, Luigina et al. “Neutrophils and clinical outcomes in patients with acute coronary syndromes and/or cardiac revascularisation. A systematic review on more than 34,000 subjects.” Thrombosis and haemostasis vol. 106,4 (2011): 591-9. doi:10.1160/TH11-02-0096

Horne, Benjamin D et al. “Which white blood cell subtypes predict increased cardiovascular risk?.” Journal of the American College of Cardiology vol. 45,10 (2005): 1638-43. doi:10.1016/j.jacc.2005.02.054

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

Leng, Sean X et al. “Baseline total and specific differential white blood cell counts and 5-year all-cause mortality in community-dwelling older women.” Experimental gerontology vol. 40,12 (2005): 982-7. doi:10.1016/j.exger.2005.08.006

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

Pahwa, Roma, et al. “Chronic Inflammation.” StatPearls, StatPearls Publishing, 8 August 2022.