Does IV Methylprednisolone Cause Elevated WBC and Neutrophil Counts?
Yes, IV methylprednisolone causes a well-established, dose-dependent increase in white blood cell count, predominantly through neutrophil elevation (neutrophilia), which can occur as early as the first day of treatment and persist throughout therapy. 1
Mechanism of Leukocytosis
The neutrophilia induced by methylprednisolone occurs through multiple mechanisms:
Demargination of neutrophils: Methylprednisolone reduces neutrophil adhesion molecule expression, specifically decreasing Mac-1 (CD11b) by 35-51% and L-selectin (CD62L) by 17-31% within 6 hours of administration. 2, 3 This causes marginated neutrophils to detach from vessel walls and enter the circulation.
Reduced neutrophil migration: The decreased expression of adhesion molecules impairs the capacity of neutrophils to migrate from the vasculature into tissues. 2
Increased granulocyte production: Methylprednisolone induces granulocyte-colony stimulating factor (G-CSF), which increases by threefold at 6 hours, contributing to neutrophil production and release from bone marrow. 2
Expected Magnitude and Timeline
Typical response pattern after IV methylprednisolone:
At 6 hours: Neutrophil counts increase approximately threefold (200-300% of baseline), with WBC rising by 23-30%. 2, 3
At 24 hours: Neutrophil counts remain elevated at approximately twofold (200% of baseline). 2
Percentage shift: The neutrophil percentage increases from baseline (e.g., from 54.6% to 58.1%). 3
Absolute increases: Expect increases of approximately 4,000-4,600 neutrophils/mm³ above baseline with doses of 200-400 mg hydrocortisone equivalent. 4
Recovery: All parameters typically return to baseline levels within 48 hours after completing a 5-day therapeutic course. 2
Clinical Implications and Pitfalls
Critical distinction from infection:
Check peripheral smear: Look specifically for left shift (>6% bands) and toxic granulation to distinguish steroid-induced leukocytosis from infection. 1
Investigate for infection if: WBC >14,000/mm³ AND left shift is present, regardless of steroid dose. 1
Magnitude matters: Even small doses of prednisone administered over prolonged periods can induce extreme and persistent leukocytosis. 1
Fever may be absent: Maintain heightened vigilance for occult infection in immunosuppressed patients on chronic steroids, even without fever, as leukocytosis may be blunted or absent in truly infected immunocompromised patients. 1
Lymphocyte effects:
Corticosteroids are lymphocyte-depleting agents, so while neutrophils increase, lymphocyte counts may decrease. 5, 1
Absolute lymphocyte and eosinophil counts typically do not change significantly or may decrease. 3
Practical Monitoring Recommendations
When patients receive IV methylprednisolone (e.g., 30 mg every 12 hours or 100 mg every 6 hours for acute severe ulcerative colitis 5, or 1 g daily for 3 days for severe immune-related adverse events 5):
Expect neutrophilia: Anticipate WBC elevation of 4,000-6,000 cells/mm³ within 6-24 hours.
Do not reflexively treat: Isolated neutrophilia without left shift, fever, or clinical signs of infection does not require antibiotics.
Serial monitoring: If infection is suspected, follow serial WBC counts with differential and assess clinical trajectory rather than relying on a single elevated value.
Consider prophylaxis: For patients on chronic high-dose steroids, consider Pneumocystis jirovecii prophylaxis and maintain vigilance for opportunistic infections. 1