EBM Consult

A General Review of the Mechanisms for Steroid or Glucocorticoid Induced Increases in the White Blood Cell (WBC) Count


  • Glucocorticoids (e.g., dexamethasone, methylprednisolone, prednisone) are known to increase the white blood cell (WBC) count upon their initiation.  The increase in WBC count is predominantly neutrophils (polymorphonuclear leukocytes; PMN).
  • The biologic effects that contribute to the increase in PMNs in the circulation are a culmination of demargination of neutrophils from the endovascular lining (about 61% of the increase), delayed migration of PMNs into tissue and rate of apoptosis (about 29%) and release of immature (bands) neutrophils from the bone marrow into the circulation (about 10%).
  • As such, it is important for clinicians to consider these effects in order to properly assess the increase in WBC counts so that a new or underlying bacterial infection is not missed.
  • Patients with glucocorticoid induced leukocytosis generally will not present with the typical "left shift" in the WBC differential seen during an acute bacterial infection, nor should they develop a fever or experience a worsening of clinical symptoms (assuming that the initial treatments are appropriate for the condition being treated).

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Last Reviewed: August 2015


  • The white blood cell (WBC) count is a routine laboratory test that reflects the number of leukocytes (or WBC) distributed in the blood.  The leukocytes that make up a typical WBC count on a lab analysis include neutrophils at 60-70%, lymphocytes at 28%, monocytes at 5%, eosinophils at 2-4%, and basophils at 0.5%.1  When a WBC count is performed, the values reflect the leukocytes distributed within the blood and not those in the bone marrow, tissue or attached to the endovascular lining of blood vessels.  It is evident that the neutrophils make up the greatest percentage of leukocytes and thus can have the greatest impact on changes in the WBC count.  Neutrophils are also called polymorphonuclear leukocytes (PMN) because of the number of stages they go through during their life cycle.  They are initially released from the bone marrow as immature neutrophils that are characterized as having a nonsegmented, band like appearing nucleus.  As such, these immature neutrophils are called "bands".  An increase in the number of these immature neutrophils in circulation can be indicative of a bacterial infection for which they are being generated to fight.  This is known as the "left shift" seen in a WBC differential.2  As the immature neutrophils become activated or exposed to bacterial pathogens, their nucleus will take on a segmented appearance due to increases gene transcription.  These and other neutrophils can be found in several compartments in the body, but the two compartments that relate most to this newsletter are the marginal compartment (those neutrophils attached to the endothelium of the blood vessel) and the circulating compartment (those circulating in the blood vessels along with other cells).  Understanding this information is critical for the proper assessment of an elevated WBC count, especially when glucocorticoids (e.g., dexamethasone, methylprednisolone, prednisone) have been administered to the patient. 

    While glucocorticoids are used to inhibit inflammation and the immune response in certain clinical situations, their initiation may also cause an increase in the WBC count.2-4  A more detailed inspection of the differential will reveal the PMNs to be the main contributors to the increase.  Since increases in PMNs can be associated with bacterial infections, the use of the WBC differential can be helpful at determining whether or not the increase in WBC count was from a bacterial infection or the initiation of glucocorticoids.  The initiation of glucocorticoids does not usually cause the same degree of a "left shift" that is normally associated with presence of a bacterial infection.3,4  In addition, glucocorticoid induced leukocytosis generally is not associated with increases in temperature or worsening of the condition being treated. Determining the cause of the WBC increase is especially important, and often more difficult, in the immunocompromised patient.  

    What are main causes of steroid induced increases in the WBC count?

    The answer is a multifactorial culmination of the following biological effects of the glucocorticoids. 

    • The greatest effect is demargination of the neutrophils from the endovascular lining.4 In short, this is where the neutrophils attached to the endothelial lining of the blood vessels become detached and are then free in circulation. As a result, when a lab is drawn via venipuncture from a patient to determine the WBC count, there will now be a greater number of circulating PMNs. However, it is important to note that the total number of PMNs has not changed, just the percentage of PMNs residing in each compartment. The demargination of neutrophils makes up approximately 61% of the increase in WBC.4 The details of how glucocorticoid administration causes demargination is described in this EBM Consult article ... click here
    • The second contributing factor is a combination of delayed migration from the circulation into the tissue and improved survival of circulating neutrophils by suppressing apoptosis (programmed cell death).4-9  These two make up approximately 29% of the increase in WBC count.4  The delayed migration into tissue is due to glucocorticoid induced down regulation of adhesion molecules on both neutrophils (i.e., L-selectin) and endothelial cells (i.e., ICAM-1, ECAM-1, Mac-1) lining the blood vessel; these normally allow neutrophils to stay attached to and facilitate transmigration through the vessel wall and into the tissue.5-7  The mechanism for delayed apoptosis is not fully known.8,9 
    • The third factor is glucocorticoid induced release of non-segmented (bands) neutrophils from the bone marrow into the general circulation.4,10 
    • This last component makes up only 10% of the increase in WBC count and thus is the reason that patients may not show as significant a "left shift" as would be seen with bacterial infections.

    It is common for patients to reveal a leukocytosis (increased WBC count) within 24 hours of initiation of a glucocorticoid.  It is important for clinicians to be aware of this expected side effect and to understand the rationale for such an increase as well as appropriate interpretation of the labs given the patient's clinical condition.  Keeping all of these things in mind will help clinicians avoid unnecessary medical work-up for other conditions and avoid patient exposure to additional drug therapy that is not warranted, such as intravenous antibiotics.

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    1. Junqueira LC, Carneiro J.  Blood cells.  In: Basic Histology.  11th ed.  Junqueira LC, Caneiro J eds.  McGraw-Hill Medical Publishing Division.  New York, NY. 2005; 223-237.
    2. Abramson N, Melton B.  Leukocytosis: basic of clinical assessment.  Am Fam Physician  2000;62:2053-60.  
    3. Shoenfeld Y, Gurewich Y, Gallant LA, et al.  Prednisone-induced leukocytosis. Influenced of dosage, method and duration of administration on the degree of leukocytosis.  Am J Med  1981;71:773-8.  
    4. Nakagawa M, Terashima T, D'yachkova Y et al.  Glucocorticoid-induced granulocytosis: contribution of marrow release and demargination of intravascular granulocytes.  Circulation  1998;98:2307-13.  
    5. Burton JL, Kehrli ME Jr, Kapil S et al.  Regulation of L-selectin and CD18 on bovine neutrophils by glucocorticoids: effects of cortisol and dexamethasone.  J Leukoc Biol  1995;57:317-25.  
    6. Waisman D, Van Eeden SF, Hogg JC et al.  L-selectin expression on polymorphonuclear leukocytes and monocytes in premature infants: reduced expression after dexamethasone treatment for bronchopulmonary dysplasia.  J Pediatr  1998;132:53-6.  
    7. Weber PS, Toelboell T, Chang LC et al.  Mechanisms of glucocorticoid-induced down-regulation of neutrophil L-selectin in cattle: evidence for effects at the gene-expression level and primarily on blood neutrophils.  J Leukoc Biol  2004;75:815-27.  
    8. Liles WC, Dale DC, Klebanoff SJ.  Glucocorticoids inhibit apoptosis of human neutrophils.  Blood  1995;86:3181-8.  
    9. Cox G.  Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes.  J Immunol  1995;154:4719-25.  
    10. Bishop CR, Athens JW, Boggs DR et al.  Leukokinetic studies. 13. A non-steady-state kinetic evaluation of the mechanism of cortisone-induced granulocytosis.  J Clin Invest  1968;47:249-60.


  • Steroid Induced WBC, Steroid Increases in the WBC, Glucocorticoid Induced Increase in WBC, Prednisone Mechanism for Rise in WBC, L-selectin, ECAM-1, ICAM-1, WBC Transmigration, Demargination