What is the neutrophil (white blood cell) to lymphocyte (white blood cell) ratio (NLR)?

What is the Neutrophil-to-Lymphocyte Ratio (NLR)?

The neutrophil-to-lymphocyte ratio (NLR) is a simple arithmetic calculation derived from a routine complete blood count that divides the absolute neutrophil count by the absolute lymphocyte count, serving as a widely available marker of systemic inflammation and immune system stress. 1

Basic Definition and Calculation

• NLR is calculated by dividing the number of circulating neutrophils by the number of circulating lymphocytes from a standard white blood cell differential count. 1
• The calculation requires no additional testing beyond a routine complete blood count with differential, making it immediately available in any clinical setting worldwide. 2
• NLR reflects the dynamic relationship between innate immunity (represented by neutrophils) and adaptive cellular immunity (represented by lymphocytes) during illness and pathological states. 1

Normal and Pathological Values

• The normal range for NLR in adults is between 1.0-2.0. 1
• Values higher than 3.0 are considered pathological and indicate significant systemic inflammation or stress. 1, 3
• Values below 0.7 in adults are also pathological and may indicate immunosuppression or bone marrow dysfunction. 1
• The "grey zone" between 2.3-3.0 serves as an early warning of developing pathological processes such as cancer, atherosclerosis, infection, inflammation, psychiatric disorders, or stress. 1

Physiological Basis

• NLR increases during stress and inflammation because stress hormones (catecholamines and cortisol) cause neutrophils to increase while simultaneously causing lymphocytes to decrease. 4
• After acute exercise or stress, lymphocytes show a biphasic pattern: they initially increase immediately after the stressor, then strongly decrease for up to 36 hours (potentially dropping 50% below baseline), while neutrophils continue to increase for 4-6 hours after the stressor ends. 4
• This differential response of white blood cell subsets creates the characteristic elevation in NLR during inflammatory states. 4

Clinical Applications and Prognostic Value

Cancer Prognosis

• The European Society for Medical Oncology recommends considering NLR as a prognostic factor in cancer patients, as NLR >3.0 correlates with poorer prognosis across various solid tumors. 5
• The European Respiratory Society incorporates NLR into the LENT score for predicting survival in patients with malignant pleural effusions. 4, 5
• NLR correlates with tumor size, stage, metastatic potential, and lymphatic invasion, and has independent prognostic value for overall survival, cancer-free survival, and cancer-specific survival. 1
• The cut-off value of NLR above 3.0 (interquartile range 2.5-5.0) has been validated across multiple meta-analyses for cancer prognosis. 1

Infection and Sepsis

• NLR is a highly sensitive indicator of infection, inflammation, and sepsis, with dramatic increases (NLR >11, ≥17, or even >30) indicating severe critical illness and high stress levels. 1
• Improving clinical course in sepsis and lower mortality risk are associated with declining NLR values below 7. 1
• Dynamic changes in NLR precede clinical deterioration by several hours, providing early warning of ongoing pathological processes. 1

Cardiovascular Disease

• In patients with atrial fibrillation, elevated NLR is associated with increased risk of major bleeding events (HR 1.60), stroke/systemic embolism (HR 1.25), myocardial infarction (HR 1.73), major adverse cardiac events (HR 1.70), cardiovascular death (HR 1.93), and all-cause mortality (HR 2.00). 2
• In chronic hemodialysis patients, higher NLR independently predicts cardiovascular mortality and is associated with increased pulse pressure, left ventricular mass index, and intima-media thickness. 6

COVID-19

• Patients with COVID-19 commonly present with elevated NLR, which correlates with disease severity, ICU admission, and acute respiratory failure. 4, 7
• Elevated NLR at admission predicts development of complications during hospitalization and need for intensive care. 7

General Medical Inpatients

• In medical inpatients with multiple chronic conditions, NLR >3.0 at both admission and discharge independently predicts 2-year mortality (OR 2.3), even after adjusting for age, sex, metastatic cancer, liver disease, depression, and previous hospitalizations. 3

Factors Influencing NLR

• NLR is influenced by age, race, medications (lithium, beta-agonists, epinephrine cause neutrophilia), chronic diseases (coronary heart disease, stroke, diabetes, obesity), psychiatric diagnoses, solid organ cancers, anemia, and stress. 1, 8
• Fitness level, nutritional status, sex, and temperature may also influence both baseline white blood cell levels and acute stress responses. 4

Clinical Utility and Limitations

• NLR is cheap, simple, fast-responding, and easily available with high sensitivity but low specificity, making it ideal for routine use in emergency departments, ICUs, and acute medicine settings including surgery, orthopedics, traumatology, cardiology, neurology, psychiatry, and oncology. 1
• NLR should be monitored serially with attention to both absolute values and dynamic trends rather than relying on a single measurement. 1
• The major limitation is that NLR has high sensitivity but low specificity—it indicates inflammation or stress but does not identify the specific cause. 1