Corticosteroids are a class of medications used widely to treat conditions involving inflammation or overactive immune responses. These drugs mimic cortisol, a naturally occurring steroid hormone, and exert a powerful influence on the immune system. An immediate consequence of their use is a significant change in the composition of circulating white blood cells (WBCs). This effect is an expected, dose-dependent pharmacological action, not a sign of a new illness, and must be recognized when interpreting blood test results.
Corticosteroids and Total White Blood Cell Count
The most common finding after starting corticosteroid therapy is an apparent increase in the total white blood cell count, known as leukocytosis. This elevation can be pronounced, sometimes suggesting an infection. The magnitude of this increase is directly related to the dose administered; for instance, high-dose regimens have been associated with an average WBC increase of up to 4.84 x 10⁹/L within 48 hours.
This increase is often referred to as a “pseudoneutrophilia” because it represents a false elevation, as the body is not necessarily producing new cells faster. Instead, the total number of circulating cells rises because of a physical redistribution of existing cells. The WBC response typically peaks approximately 48 hours after the steroid is administered, demonstrating the rapid onset of this medication effect.
The Mechanism of Immune Cell Redistribution
The increase in the total WBC count is driven by the steroid’s influence on how immune cells move throughout the vascular system. White blood cells, particularly neutrophils, exist in two main pools within the blood vessels: the circulating pool and the marginal pool. The marginal pool consists of cells loosely attached to the inner lining of the vessel walls, ready to migrate into tissues to fight infection.
Corticosteroids inhibit the adhesion molecules that allow these cells to stick to the vessel walls. By reducing the expression of these molecules, the cells detach and are flushed from the marginal pool back into the circulating blood volume. This process, known as “demargination,” is the primary factor contributing to the observed rise in total WBCs, accounting for approximately 60% of the neutrophil increase.
Steroids also delay the ability of neutrophils to exit the bloodstream and move into surrounding tissues, a process called transmigration. This delay effectively keeps the cells trapped in the circulation for a longer period. Furthermore, corticosteroids extend the lifespan of neutrophils by inhibiting apoptosis, or programmed cell death, which further contributes to the higher measurable count. These combined mechanisms of demargination, delayed migration, and prolonged survival account for the measurable increase in circulating white blood cells.
Differential Changes in Specific WBC Types
The specific, differential change among the five main types of white blood cells creates a characteristic “steroid signature.” The most dramatic effect is an increase in neutrophils, known as neutrophilia, due to the redistribution and prolonged survival mechanisms.
Corticosteroids cause a decrease in other types of white blood cells. This includes a notable reduction in lymphocytes, resulting in lymphopenia, as the steroids cause lymphocytes to move out of the blood and sequester in lymphoid tissues. Eosinophils are also significantly suppressed, leading to eosinopenia, and monocytes often show a variable degree of decrease.
This specific pattern—high neutrophils coupled with low lymphocytes and eosinophils—is a predictable pharmacological response. While steroids stimulate a small release of immature neutrophils, known as band forms, from the bone marrow, this release is not usually significant enough to cause the “left shift” typically seen in a true bacterial infection.
Interpreting Steroid-Induced Changes
The most significant clinical challenge posed by steroid-induced leukocytosis is that the elevated total WBC count can mimic a bacterial infection. Without considering steroid use, a physician might incorrectly initiate unnecessary antibiotic treatment. The specific differential pattern, however, provides the necessary distinction for proper interpretation.
A true bacterial infection typically causes an increase in neutrophils but maintains a normal or high lymphocyte count. The steroid signature of high neutrophils and low lymphocytes helps doctors differentiate the medication effect from a true infectious process. Clinicians should also consider the magnitude of the increase, as an elevation significantly greater than the expected increase seen with high-dose therapy may suggest an alternative cause for the leukocytosis.
Steroid-induced leukocytosis is generally not accompanied by other typical signs of infection, such as fever. When interpreting results, doctors factor in the expected increase and look for other markers, like a significant “left shift” or the appearance of toxic granulation in the neutrophils, which are more indicative of a genuine infection.