What Medications Increase Leukocytes? Understanding Drug-Induced Leukocytosis

October 12, 2025 •

3 min read

Approximately 5.7% of hospitalized nonsurgical patients receiving steroids develop leukocytosis, with the degree often linked to the dosage. This highlights how certain medications increase leukocytes, or white blood cells, a condition known as drug-induced leukocytosis. It's a common side effect of many therapeutic drugs and often resolves once the medication is discontinued.

Quick Summary

An increase in white blood cell count can be a side effect of various medications, such as corticosteroids, lithium, and colony-stimulating factors (G-CSFs). It often occurs due to changes in how the bone marrow releases and manages these immune cells.

Key Points

Corticosteroids are a frequent cause: Drugs like prednisone commonly increase leukocytes, primarily neutrophils, by altering their release and movement in the body.
Lithium can cause persistent leukocytosis: The psychiatric drug lithium carbonate is known to cause a sustained increase in white blood cell count throughout treatment.
G-CSFs are specifically designed to increase WBCs: Medications like filgrastim (Neupogen) and pegfilgrastim (Neulasta) are therapeutic agents used to deliberately stimulate the production of neutrophils.
Leukocytosis varies by drug and mechanism: While steroids cause a demargination and delayed apoptosis, lithium stimulates bone marrow production, and other drugs like beta-agonists can also have transient effects.
Context is crucial for diagnosis: Interpreting an elevated WBC count requires considering a patient's medication history, as drug-induced leukocytosis must be differentiated from more serious causes like infection or malignancy.
The WBC differential provides important clues: Corticosteroid-induced leukocytosis typically shows neutrophilia with low lymphocytes and eosinophils, a key contrast to many infection-related increases.

Leukocytosis is a condition defined by an abnormally high white blood cell (WBC) count in the blood, typically exceeding 11,000 cells per microliter. While often a natural response to infection or inflammation, it can also be a side effect of various medications. For clinicians, differentiating drug-induced leukocytosis from a more serious pathological cause like infection or leukemia is a critical diagnostic challenge. Understanding the specific medications and their mechanisms is essential for accurate interpretation of a patient's blood work.

Corticosteroids: A Common Culprit

Corticosteroids, such as prednisone and dexamethasone, are one of the most common causes of drug-induced leukocytosis. This is often a neutrophilic leukocytosis, meaning the increase is primarily due to neutrophils, a specific type of white blood cell. The mechanism involves several key actions:

Demargination: Corticosteroids cause neutrophils that are typically 'parked' along the walls of blood vessels to detach and enter the main circulation.
Delayed Migration: They inhibit the movement of neutrophils from the bloodstream into tissues, trapping them in circulation for longer periods.
Increased Release: Steroids can stimulate the bone marrow to release more neutrophils into the blood.
Delayed Apoptosis: They can prolong the life of existing neutrophils by delaying programmed cell death.

Studies show that the magnitude of leukocytosis is often dose-dependent, with higher doses causing a more significant increase. The WBC count typically peaks around 48 hours after administration and gradually declines thereafter.

Lithium's Role in Increasing Leukocytes

Lithium carbonate, a medication used to treat bipolar disorder and other psychiatric conditions, is also well-known for causing leukocytosis. In many patients, this effect is persistent throughout treatment. For some individuals, the increase is significant enough that lithium has been explored as a treatment for drug-induced leukopenia (low WBC count). Unlike corticosteroids, lithium's effect on WBCs is less understood but is known to involve stimulating the bone marrow to produce more leukocytes.

Therapeutic Colony-Stimulating Factors (G-CSFs)

Granulocyte-colony stimulating factors (G-CSFs) are a class of medications specifically designed to increase the number of white blood cells, particularly neutrophils. These are not a side effect, but rather the intended therapeutic purpose of the drug. Examples include filgrastim (brand names Neupogen, Zarxio, Nivestym) and its long-acting form, pegfilgrastim (Neulasta). G-CSFs work by stimulating the bone marrow to produce and release more neutrophils, a critical strategy for patients undergoing chemotherapy or those with severe neutropenia.

Other Medications Implicated in Leukocytosis

Several other medication classes have been reported to cause an increase in WBC counts, including:

Beta-agonists: Drugs like albuterol can cause a temporary leukocytosis through demargination of white blood cells.
Epinephrine: Similar to beta-agonists, epinephrine can cause a transient increase in WBC counts.
Select Antibiotics and Anticonvulsants: Some reports implicate certain types of antibiotics and anticonvulsants, although the mechanisms are often less defined.
Allopurinol: This medication, used for gout, can also cause an elevated WBC count.

Comparison: Drug-Induced vs. Pathological Leukocytosis

Determining the cause of leukocytosis involves considering the clinical context, lab results, and medication history. The following table highlights key differences between drug-induced and pathological leukocytosis:


Feature	Drug-Induced Leukocytosis (e.g., Corticosteroid)	Pathological Leukocytosis (e.g., Infection)
Onset	Occurs shortly after medication initiation, often peaking within 48 hours.	Can occur rapidly with acute infection or gradually with chronic conditions.
WBC Differential	Typically neutrophilia with reduced lymphocytes, monocytes, and eosinophils.	Varies based on pathogen (e.g., neutrophilia for bacteria, lymphocytosis for viruses).
Cell Morphology	Generally, cells appear mature and normal, lacking features like toxic granulation.	Often presents with immature cell forms ('shift to the left') or toxic granulation.
Clinical Symptoms	Unaccompanied by typical infection symptoms like fever, chills, or worsening malaise.	Accompanied by other signs of infection or inflammation.
Resolution	Resolves once the medication is tapered or discontinued.	Resolves as the underlying infection or inflammation is treated.

Conclusion: The Importance of Context

Numerous medications can cause an increase in leukocytes, and distinguishing between a benign drug effect and a more serious condition is crucial. Understanding how and when medications like corticosteroids, lithium, and G-CSFs affect white blood cell counts is a vital part of clinical practice. Always provide your complete medication history to your healthcare provider, as this information is essential for interpreting laboratory results correctly. While a high WBC count can be a normal immune response, persistent and unexplained elevations warrant further medical investigation to rule out other underlying causes.

For more information on the various causes of leukocytosis, consult the StatPearls article on Leukocytosis.

Frequently Asked Questions

Corticosteroids (e.g., prednisone, dexamethasone), lithium carbonate, and colony-stimulating factors (G-CSFs) such as filgrastim are among the most common medications known to increase white blood cell counts.

Steroids increase white blood cell counts primarily by causing neutrophils to detach from blood vessel walls (demargination), delaying their migration into tissues, and increasing their release from the bone marrow. This traps more neutrophils in the circulating blood.

Drug-induced leukocytosis is not typically dangerous on its own, but it can complicate the diagnosis of other conditions like infection or inflammation. It is important for healthcare providers to be aware of your medications to interpret blood test results correctly.

Drug-induced leukocytosis is managed by treating the underlying condition for which the medication was prescribed. It often resolves on its own once the medication is tapered or discontinued, so specific treatment is not usually necessary unless the WBC count becomes excessively high.

Some over-the-counter medications, like certain NSAIDs, have been implicated in causing leukocytosis, though this is less common and often less pronounced than with prescription drugs like corticosteroids. It is always best to discuss all medications with your doctor.

Leukocytosis from infection often involves immature white blood cells and is accompanied by other symptoms like fever. In contrast, drug-induced leukocytosis (particularly from steroids) usually consists of mature, normal-looking white blood cells and lacks typical signs of infection.

G-CSF stands for granulocyte-colony stimulating factor. These are a class of medications, including filgrastim (Neupogen) and pegfilgrastim (Neulasta), used specifically to stimulate the bone marrow to produce more neutrophils, particularly in patients undergoing chemotherapy or with severe chronic neutropenia.