Does prednisone (corticosteroid) elevate neutrophil counts?

Prednisone Elevates Neutrophils

Yes, prednisone consistently elevates neutrophil counts through multiple mechanisms, producing a dose-dependent neutrophilia that begins within 6-24 hours and persists throughout treatment. 1

Mechanism of Neutrophil Elevation

Prednisone causes neutrophilia through several well-established pathways:

• Demargination of neutrophils from the vascular endothelium into circulation, accounting for the rapid onset of leukocytosis 2
• Down-regulation of adhesion molecules (L-selectin reduced by 40%, Mac-1 reduced by 35%), which decreases neutrophil capacity to migrate out of the vasculature 2
• Induction of granulocyte-colony stimulating factor (G-CSF), which increases neutrophil production and release from bone marrow (G-CSF levels increase threefold at 6 hours) 2
• Mobilization of bone marrow neutrophil reserves, demonstrating that corticosteroids can be used equivalently to endotoxin for measuring neutrophil reserve response 3

Magnitude and Timing of Response

The neutrophil elevation follows predictable patterns:

• Dose-response relationship: Prednisone doses of 40-80 mg produce approximately 4,000-4,600 cells/mm³ increase in neutrophil count 3
• Rapid onset: Neutrophilia appears within 6-24 hours of first dose, with peak elevation (threefold increase) at 6 hours 1, 2
• Sustained effect: Elevation persists throughout treatment duration, even with prolonged courses 1
• Lower doses still effective: Even small doses of prednisone administered over prolonged periods can induce extreme and persistent leukocytosis 1

Clinical Implications for Infection Diagnosis

The key challenge is distinguishing steroid-induced neutrophilia from infection-related leukocytosis. 1

When to Suspect Infection Despite Steroid Use

Investigate for infection when: 1

• WBC >14,000/mm³ with left shift (>6% bands), regardless of steroid dose
• Band neutrophil percentage >16% (likelihood ratio 4.7 for bacterial infection) 4
• Neutrophil percentage >90% (likelihood ratio 7.5 for bacterial infection) 4
• Total band count >1,500 cells/mm³ (high likelihood for documented bacterial infection) 4

Distinguishing Features

Check the peripheral smear for: 1

• Left shift (increased immature neutrophils/bands)
• Toxic granulation (indicates active infection rather than steroid effect)
• Clinical context: fever, localizing symptoms, elevated inflammatory markers beyond expected steroid effect

Steroid-induced neutrophilia typically shows mature neutrophils without left shift or toxic granulation. 1

Duration-Based Risk Stratification

The American Gastroenterological Association provides clear risk categories: 1

• Low risk (<1 week at any dose): Produces measurable leukocytosis but carries low risk for significant immunosuppression
• Moderate risk (≥4 weeks at low dose): Sustained leukocytosis with moderate risk for viral reactivation in certain populations
• High risk (≥4 weeks at ≥20 mg/day prednisone): Sustained leukocytosis with increased infection risk, warranting Pneumocystis jirovecii prophylaxis and heightened infection surveillance

Monitoring Recommendations

For patients on prednisone with elevated neutrophils: 1

• Serial WBC monitoring with differential is necessary if infection is suspected, rather than relying on a single elevated value
• Consider PCP prophylaxis for patients on chronic high-dose steroids (≥20 mg/day for ≥4 weeks)
• Maintain heightened vigilance for opportunistic infections, even without fever
• Recognize that leukocytosis may be blunted in some immunocompromised patients, making infection diagnosis more challenging

Common Pitfall

The most critical error is attributing all neutrophilia to steroid effect and missing concurrent infection. 1 A 2010 cohort study of 809 hospitalized glucocorticoid users found that observed neutrophilia was often associated with underlying disease rather than glucocorticoid use itself, particularly within diagnostic subgroups. 5 This emphasizes the importance of clinical context—always assess for infection markers (left shift, toxic granulation, fever, localizing symptoms) rather than assuming steroid effect alone.