Does prednisone (corticosteroid) increase white blood cell (WBC) and neutrophil counts?

Does Prednisone Increase WBC and Neutrophils?

Yes, prednisone consistently increases both total white blood cell count and absolute neutrophil count in a dose-dependent manner, with effects beginning within hours of administration and persisting throughout therapy. 1, 2

Mechanism and Pattern of Leukocytosis

Prednisone causes leukocytosis through its action as a lymphocyte-depleting agent, resulting in a characteristic pattern of neutrophilia with lymphopenia. 1 The increase is predominantly due to a rise in polymorphonuclear neutrophils, which coincides with monocytosis, eosinopenia, and variable lymphopenia. 2

Magnitude and Timing of WBC Elevation

Onset and Peak Response

• WBC elevation begins as early as 2-3 hours after oral administration, with peak response occurring at 48 hours. 3, 4
• The neutrophil count can increase by approximately 4,000 cells/mm³ with moderate-to-high doses. 5
• Even the first day of treatment can produce WBC counts exceeding 20,000/mm³, an increase that persists for the duration of therapy. 2

Dose-Dependent Effects

The magnitude of leukocytosis correlates directly with prednisone dose: 3

• Low-dose steroids: Mean increase of 0.3 × 10⁹/L WBCs
• Medium-dose steroids: Mean increase of 1.7 × 10⁹/L WBCs
• High-dose steroids: Mean increase of 4.84 × 10⁹/L WBCs (within 48 hours)

Doses as low as 5-10 mg daily can produce measurable leukocytosis, though the effect is more pronounced with higher doses (40-80 mg daily). 5, 6

Duration and Persistence

Even small doses of prednisone administered over prolonged periods can induce extreme and persistent leukocytosis. 2 The WBC count typically reaches maximal values within two weeks, after which it may decrease slightly but does not return to pretreatment levels while therapy continues. 2

The American Gastroenterological Association notes that corticosteroid therapy at any dose for less than 1 week produces measurable leukocytosis, while moderate-to-high dose prednisone for 4 weeks or more produces sustained leukocytosis. 1

Clinical Implications: Distinguishing from Infection

Key Differentiating Features

The critical pitfall is misinterpreting steroid-induced leukocytosis as infection. To distinguish between the two: 1, 2

• Left shift (>6% band forms) and toxic granulation strongly suggest infection rather than steroid effect, as these features are rare in corticosteroid-induced leukocytosis. 2
• The American College of Physicians recommends investigating for infection in patients with WBC >14,000/mm³ AND left shift (>6% bands), regardless of steroid dose. 1
• Serial WBC monitoring with manual differential is more informative than single values when infection is suspected. 1

Interpreting WBC Increases on Steroids

When evaluating a patient already on prednisone: 3

• Increases up to 4.84 × 10⁹/L cells within 48 hours after high-dose steroids are expected
• Any increase after low-dose steroids, or larger increases than expected for the dose, suggest other causes of leukocytosis (particularly infection)
• Individual patient responses are reproducible for a given dose, but vary significantly between patients. 4

Specific Cell Line Effects

Neutrophils

Absolute neutrophil counts increase substantially and account for the majority of WBC elevation. 2, 6 This neutrophilia begins within hours and persists throughout therapy. 6

Lymphocytes

Lymphocyte counts show a biphasic pattern: an initial rapid decrease followed by a rebound to increased levels. 6 Overall, lymphopenia is characteristic of steroid therapy. 1, 2

Eosinophils

Eosinopenia occurs consistently with prednisone administration. 2, 6

Monocytes

Monocytosis accompanies the neutrophilia. 2

Practical Monitoring Recommendations

• Obtain WBC with manual differential before morning steroid dose to avoid misinterpretation of steroid-induced changes. 4
• For patients on chronic steroids with suspected infection, assess for left shift and toxic granulation on peripheral smear. 1, 2
• Maintain heightened vigilance for occult infection in immunosuppressed patients on chronic steroids, even without fever. 1
• Consider PCP prophylaxis for patients on prednisone ≥20 mg/day for ≥4 weeks. 1