Does prednisone (corticosteroid) suppress white blood cell (WBC) count?

Prednisone Increases WBC Count, Not Suppresses It

Prednisone causes leukocytosis (elevated WBC count), not suppression—this is a dose-dependent effect that occurs as early as the first day of treatment and persists throughout therapy, predominantly due to neutrophilia. 1, 2

Mechanism of Corticosteroid-Induced Leukocytosis

• Corticosteroids are lymphocyte-depleting agents that paradoxically increase total WBC count by causing neutrophil demargination from blood vessel walls and reducing neutrophil migration to tissues, resulting in a net increase in circulating white blood cells. 1

• The leukocytosis pattern is characterized by:

  • Neutrophilia (increased neutrophils) 1, 2
  • Lymphopenia (decreased lymphocytes) 2
  • Monocytosis (increased monocytes) 2
  • Eosinopenia (decreased eosinophils) 2

Magnitude and Timing of WBC Elevation

• WBC count can increase by 2.4 × 10⁹/L at 48 hours after steroid administration, with peak effects occurring within the first 2 days. 3

• Dose-dependent response:

  • Low-dose steroids: mean increase of 0.3 × 10⁹/L 3
  • Medium-dose steroids: mean increase of 1.7 × 10⁹/L 3
  • High-dose steroids: mean increase of 4.84 × 10⁹/L 3

• Even small doses of prednisone administered over prolonged periods can induce extreme and persistent leukocytosis, with WBC counts exceeding 20,000/mm³ as early as the first day of treatment. 2

• Maximal leukocytosis typically occurs within 2 weeks, after which WBC counts may decrease slightly but remain elevated above baseline throughout therapy. 2

Clinical Implications: Distinguishing Steroid Effect from Infection

The critical challenge is differentiating corticosteroid-induced leukocytosis from infection-related leukocytosis, particularly in immunocompromised patients. 1, 2

Key Diagnostic Features:

• Investigate for infection when WBC >14,000/mm³ with left shift (>6% band forms), regardless of steroid dose. 1

• Peripheral smear findings help distinguish infection from steroid effect:

  • Infection typically shows: left shift (>6% bands) and toxic granulation 1, 2
  • Steroid-induced leukocytosis typically shows: mature neutrophils without left shift or toxic granulation 2

• Any WBC increase after low-dose steroids, or increases exceeding 4.84 × 10⁹/L after high-dose steroids, suggest alternative causes such as infection. 3

Context-Specific Monitoring

• In inflammatory bowel disease patients, glucocorticoids increase WBC count while other immunosuppressive drugs (azathioprine, 6-mercaptopurine) decrease WBC count. 4

• Serial WBC monitoring with differential is necessary if infection is suspected in patients on high-dose steroids, rather than relying on a single elevated value. 1

• C-reactive protein (CRP) levels decrease with prednisone treatment (mean reduction of 46% by days 3-7), while procalcitonin (PCT) levels remain unaffected and may better reflect true infection status. 5

Important Caveats

• Individual patient responses to steroids are highly variable but reproducible in the same patient with the same dose—WBC increases can range from -600 to +8,000/mm³ with no clear correlation to steroid dose. 6

• Leukocytosis may be blunted or absent in severely immunocompromised patients, making infection diagnosis more challenging in this population. 1

• Maintain heightened vigilance for occult infection even without fever in patients on chronic steroids, as typical inflammatory responses may be masked. 1