Do Steroids Increase Neutrophils? A Look at the “How”

Glucocorticoids, the class of steroids most commonly prescribed for inflammation and immune suppression, reliably push neutrophil counts upward in the blood. They do so not by manufacturing more neutrophils from scratch but primarily by reshuffling where existing neutrophils sit in the body. The rise can be dramatic enough to mimic an infection on a routine blood panel, and understanding the mechanisms behind it matters for anyone interpreting lab results while on prednisone, dexamethasone, or similar drugs.

The Biggest Contributor Is Demargination

Under normal conditions, roughly half of all circulating neutrophils are not actually flowing freely through the bloodstream. They are loosely stuck to the inner walls of blood vessels, particularly in the lungs, spleen, and liver, in what immunologists call the “marginated pool.” Think of them as parked along the highway rather than driving on it. When glucocorticoids enter the picture, a large fraction of those parked neutrophils peel off and rejoin the flowing traffic. This process, called demargination, is the single largest reason your neutrophil count goes up after a steroid dose.

A study using labeled neutrophils in a dexamethasone model found that demargination accounted for roughly 61% of the total rise in circulating granulocytes, with a longer half-life in the bloodstream contributing about 29% and fresh release from bone marrow making up the remaining 10% or so.¹ Those proportions help explain why the neutrophil rise happens so fast: you are not waiting for new cells to be built, you are simply moving existing ones into the lane where the blood draw can detect them.

Research using microfluidic models of capillary beds has added a physical explanation for how this works. Glucocorticoids reorganize the structural scaffolding inside neutrophils, specifically a protein mesh called cortical actin, making the cells measurably softer. Softer cells pass through narrow capillaries more easily instead of getting temporarily stuck along vessel walls. Computational modeling suggests that this reduction in stiffness alone is enough to account for the demargination effect.²

How Adhesion Molecules Get Turned Down

Neutrophils stick to vessel walls because surface proteins on the cells latch onto matching proteins on the blood vessel lining. Two of the most important are L-selectin, which handles the initial rolling contact, and CD11b/CD18 (also called Mac-1), which anchors the cell more firmly. Glucocorticoids interfere with both.

After methylprednisolone infusion, researchers found that L-selectin and Mac-1 expression on circulating neutrophils dropped, reducing the cells’ ability to grip vessel walls and migrate out of the bloodstream.³ In a related set of experiments with dexamethasone, the drug did not change these adhesion molecules on resting neutrophils, but it significantly blunted the upregulation that normally happens when neutrophils are activated by inflammatory signals. The suppression was dose-dependent, meaning more steroid produced a stronger dampening of adhesion molecule expression.⁴

The practical upshot is twofold. Neutrophils already marginated along vessel walls lose their grip and re-enter the flowing blood (adding to the count). And neutrophils that are already circulating have a harder time latching on and squeezing out of blood vessels to reach tissues where inflammation is happening. Both effects drive the neutrophil count upward on a standard lab panel, because the lab only measures what is in the blood, not what is parked along the vessel wall or sitting in tissue.

Bone Marrow Kicks In a Smaller Boost

Your bone marrow keeps a reserve of mature neutrophils ready for deployment. Glucocorticoids stimulate the release of these stored cells into the bloodstream, adding another layer to the rising count.⁵ While this contribution is real, the rabbit dexamethasone study described earlier estimated it accounts for only about a tenth of the total increase. That makes sense intuitively: bone marrow has to push cells through several layers of tissue and into the bloodstream, a slower process than simply loosening cells that are already inside blood vessels.

A related and less well-studied question is whether steroids can push immature neutrophils, called band cells, into the blood. Band cells normally appear during serious infections, so their presence on a blood smear raises alarm bells. A case report documented bandemia after a single high dose of dexamethasone in an otherwise healthy patient without infection or inflammation, though the authors noted that formal studies in humans specifically examining steroid-induced bandemia have not been done.⁵ That gap in the evidence is worth keeping in mind: most of what we know about steroids and neutrophils focuses on mature cells.

Neutrophils Live Longer Under Glucocorticoids

Neutrophils are short-lived cells. In the bloodstream, their normal lifespan is measured in hours, after which they undergo a programmed cell death called apoptosis and are cleared away. Glucocorticoids slow this self-destruct sequence considerably.

In lab cultures, dexamethasone, methylprednisolone, and hydrocortisone all inhibited neutrophil apoptosis by 59% to 90% over time points ranging from 12 to 48 hours. The drugs reduced the DNA fragmentation that marks a dying cell and kept neutrophils viable well beyond their usual expiration date.⁶ A separate group confirmed that four different glucocorticoids caused dose-dependent apoptosis inhibition, with dexamethasone showing the strongest effect, and observed that the surviving neutrophils remained functionally responsive rather than just lingering in a dormant state.⁷

This delayed cell death has a double-edged quality. In the bloodstream, it means more neutrophils are circulating at any given moment because fewer are dying off. But in tissues, lingering neutrophils can continue releasing enzymes and reactive oxygen species, potentially causing collateral damage. The researchers flagged this as potentially “detrimental in vivo” because slower clearance of neutrophils from tissues could worsen the very inflammation the steroids were prescribed to treat.⁸

Putting the Mechanisms Together

The three mechanisms work in concert and on overlapping timelines. Demargination and reduced extravasation shift neutrophils into the circulating blood quickly, within hours. Bone marrow release adds a smaller pulse of fresh cells. And delayed apoptosis keeps all of those neutrophils circulating longer than they otherwise would. The net effect is a sharp, dose-dependent jump in the absolute neutrophil count that the body did not produce by ramping up neutrophil manufacturing.

At the molecular level, glucocorticoids do all this by binding to an intracellular receptor known as the glucocorticoid receptor, which then moves into the cell nucleus and alters gene expression. The receptor-steroid complex turns up anti-inflammatory genes and turns down pro-inflammatory ones, which is the familiar anti-inflammatory action of steroids.⁹ But glucocorticoids also act through faster, non-genomic pathways that do not require changes in gene expression, which helps explain why demargination starts so rapidly after a dose.¹⁰

More Neutrophils, but Less Neutrophil Function

Here is one of the more counterintuitive aspects of steroid-induced neutrophilia: while the count goes up, neutrophil function often goes down. Glucocorticoids exert broad inhibitory effects on the things neutrophils actually do, including chemotaxis (the ability to migrate toward an infection), adhesion, transmigration through vessel walls, the oxidative burst (the chemical attack neutrophils use to kill microbes), and phagocytosis (engulfing pathogens).¹¹ So you have more neutrophils in the blood, but each one is somewhat hobbled. This is relevant for people on chronic steroids who are already at increased risk of infection. Their blood work may look reassuringly normal or even elevated in neutrophils, yet their immune defense against invading pathogens is compromised.

How Fast and How High the Count Climbs

The neutrophil rise is not subtle, and it happens quickly. A study of noninfected hospitalized patients found that white blood cell counts peaked about 48 hours after steroid administration across all dose levels. In patients receiving high-dose steroids, the average increase from baseline was roughly 4.8 × 10⁹/L, while medium doses produced an average increase of about 1.7 × 10⁹/L. Low doses caused a much smaller bump of about 0.3 × 10⁹/L that barely differed from baseline by the third day.¹² The absolute neutrophil count specifically followed the same dose-response pattern, peaking on day two and then drifting back toward baseline.¹²

An older study of patients on prednisone reported even more dramatic numbers in some cases, with white blood cell counts surpassing 20,000 per cubic millimeter as early as the first day of treatment and staying elevated for the duration of therapy.¹³ The variability between individuals is considerable, so a single “expected” number is misleading. What is consistent is that the rise is predominantly in neutrophils and is dose-dependent.

In patients with acute infections who are also receiving steroids, the picture gets more complicated. One study found that the overall peak white blood cell count was higher in patients on acute steroid therapy (about 15.4 × 10⁹/L) compared to those not on steroids (about 12.9 × 10⁹/L), with chronic steroid users falling in between. In chronically treated patients with infections, the average bump attributable to the steroid itself was roughly 5 × 10⁹/L.¹⁴

Telling Steroid-Induced Neutrophilia from Infection

This is the question that matters most in clinical practice. A patient on steroids walks in with a high white blood cell count dominated by neutrophils. Is that count just the steroid effect, or does it mean infection? Clinicians have wrestled with this for decades, and a few features help.

The classic teaching point is that steroid-induced leukocytosis typically lacks a “left shift,” meaning there should be few or no band cells (immature neutrophils) and no toxic granulation in the neutrophils. In genuine bacterial infection, you tend to see band forms exceeding about 6% of the differential along with toxic-appearing granules in the cytoplasm. Early research on prednisone-induced leukocytosis specifically noted that a left shift and toxic granulation could help distinguish infection from steroid effect, since the latter rarely produced them.¹³ That said, the case report of dexamethasone-induced bandemia mentioned earlier complicates this rule of thumb, at least for high single doses.

Beyond the blood smear, the pattern of other white blood cells provides clues. Steroids tend to push lymphocyte and eosinophil counts down while raising neutrophils and, to a lesser degree, monocytes. So a high neutrophil count with low lymphocytes, low eosinophils, and no left shift is a signature more consistent with steroids than with bacterial infection, where eosinophils often drop as well but lymphocytes may not follow the same steroid-induced pattern. One study of cancer patients taking steroids at the start of immunotherapy documented significantly higher neutrophil counts and lower eosinophil counts compared to patients not on steroids, a pattern that persisted at four weeks.¹⁵

Endogenous Cortisol Produces the Same Effect

You do not need a prescription to experience steroid-induced neutrophilia. Your adrenal glands produce cortisol, a natural glucocorticoid, every day, with a surge in the early morning hours. Physical stress, surgery, critical illness, and emotional stress all trigger additional cortisol release. This is part of why blood counts taken in the morning or after a stressful event may show mildly elevated neutrophils without any pathology.

In conditions where the body overproduces cortisol chronically, such as Cushing’s disease, sustained neutrophilia is a recognized feature. A review of neutrophilia in subclinical Cushing’s disease noted that glucocorticoids increase both the marginal-pool and circulating-pool granulocyte counts, unlike catecholamines (adrenaline), which only move cells from the marginated pool into circulation.¹⁶ In other words, cortisol both makes more neutrophils available overall and redistributes them into the measurable compartment, while adrenaline only does the redistribution part. This distinction can matter when interpreting blood work from a stressed or critically ill patient who is also receiving exogenous steroids.

What About Anabolic Steroids and Testosterone

When most people say “steroids,” they might mean either corticosteroids (prednisone, dexamethasone, hydrocortisone) or anabolic-androgenic steroids (testosterone, nandrolone, and their synthetic relatives). The mechanisms described throughout this article apply to glucocorticoids. But testosterone has its own effects on neutrophils, and they are not trivial.

In two clinical trials, testosterone administration in men was associated with dose-dependent increases in total leukocyte counts and, specifically, absolute neutrophil counts. At higher doses, the neutrophil increase was substantial, around 1,100 to 1,200 cells per microliter above baseline. Testosterone did not, however, affect lymphocyte counts.¹⁴ The mechanism appears different from glucocorticoid-driven neutrophilia. Testosterone is known to stimulate bone marrow activity broadly, including red blood cell production, and the neutrophil rise likely reflects enhanced myelopoiesis (the creation of new white blood cells in the marrow) rather than the demargination-heavy mechanism of glucocorticoids. So if you are on testosterone replacement therapy or using anabolic steroids and notice a higher neutrophil count, the cause is real but the underlying biology differs from what prednisone does.

When Steroid-Induced Neutrophilia Leads to Unnecessary Treatment

The most practical concern with steroid-induced neutrophilia is that it gets mistaken for infection, triggering unnecessary antibiotics, additional imaging, extended hospital stays, or invasive workups. A patient admitted for an asthma exacerbation who receives high-dose methylprednisolone and then shows a white cell count of 18,000 the next morning might get started on broad-spectrum antibiotics “just in case.” Conversely, a genuinely infected patient on chronic prednisone might have their rising count dismissed as a steroid artifact.

The timing and pattern of the count change are the most useful tools for sorting this out. As noted, the steroid effect peaks around 48 hours and then trends back toward baseline if the dose is not repeated. A count that continues climbing beyond day two, especially with an emerging left shift, deserves a closer look for infection. And the accompanying drops in lymphocytes and eosinophils that steroids produce are a helpful fingerprint. Clinicians who know what to expect from steroid-driven blood count changes can spare patients a good deal of unnecessary intervention while staying alert to the genuine infections that steroids can mask.