What is the biological mechanism by which steroids, such as prednisone, elevate white blood cell (WBC) count?

Biological Mechanism of Steroid-Induced Leukocytosis

Steroids like prednisone elevate white blood cell counts primarily by decreasing the expression of neutrophil adhesion molecules (Mac-1 and L-selectin), causing demargination of neutrophils from blood vessel walls into circulation.

Mechanism of Action

Corticosteroids cause leukocytosis through several mechanisms:

1. Demargination of neutrophils:

   • Steroids reduce the expression of adhesion molecules on neutrophils, particularly:
     • Mac-1 (CD11b) - decreased by up to 51% 1
     • L-selectin (CD62L) - decreased by up to 31% 1
   • This decreased adhesion causes neutrophils to detach from blood vessel walls and enter circulation

2. Delayed apoptosis of neutrophils:

   • Steroids extend the lifespan of circulating neutrophils
   • This contributes to the increased neutrophil count observed

3. Bone marrow effects:

   • Increased release of mature neutrophils from bone marrow storage pools
   • Enhanced neutrophil production over time with continued steroid use

Magnitude and Timing of Response

The leukocytosis response to steroids is:

• Dose-dependent: Higher doses produce greater increases in WBC count

  • 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 2

• Time-dependent:

  • Begins within hours of administration
  • Peaks at approximately 48 hours after administration 2
  • With prolonged use, WBC counts may reach maximal values within two weeks 3

Differential Effects on WBC Types

Steroids cause:

• Predominant neutrophilia - the main contributor to leukocytosis
• Monocytosis - modest increase in monocyte count
• Eosinopenia - decrease in eosinophil count
• Variable lymphopenia - often decreased lymphocyte count 3

Clinical Implications

• Even low doses of prednisone administered over prolonged periods can induce significant and persistent leukocytosis 3
• In hospitalized patients without infection, increases of up to 4.84 × 10⁹/L cells may be seen within 48 hours after high-dose steroids 2
• Larger increases, particularly after low-dose steroids, should prompt investigation for other causes of leukocytosis such as infection

Clinical Distinction from Infection-Induced Leukocytosis

When differentiating steroid-induced leukocytosis from infection:

• Steroid-induced leukocytosis rarely shows a significant "left shift" (>6% band forms)
• Toxic granulation in neutrophils is uncommon in steroid-induced leukocytosis but common in infection 3

Understanding this mechanism is important for clinicians when interpreting WBC counts in patients receiving steroid therapy, as it may prevent unnecessary investigations or treatments for suspected infection.