EBM Consult

The Average Time of Onset for Increases in the White Blood Cell (WBC) After Starting Steroids (Glucocorticoids


  • Neutrophilic demargination from the endothelial lining of the blood vessels is known to be one of the main contributors to the increase in white blood cell (WBC) counts seen with the administration of glucocorticoids.
  • Demargination occurs from the steroids ability to decrease gene transcription for L-selectin that would be used to replace shed L-selectin adhesion molecules from the surface of neutrophils that are traveling along the endothelial surface of the blood vessel.
  • Since gene transcription is likely the main cause, this biologic effect is delayed and may not manifest on a WBC count for at least 5-24 hours post glucocorticoid administration.

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Jon D. Herrington, PharmD, BCPS, BCOP

Last Reviewed: February 2018


  • It is well known that glucocorticoids (e.g., dexamethasone, methylprednisolone, prednisone) cause increases in the white blood cell (WBC) count.1-9  Upon further evaluation of the increased WBC count, it is an increase in neutrophils that primarily contribute to this effect.  In addition, it is known that of all of the mechanisms for glucocorticoid induced increases in neutrophils, it is their demargination from the endovascular lining of the blood vessel that predominates.  Upon demargination, neutrophils are then distributed into the general blood circulation where they can now show up in the venipuncture sample drawn in a standard lab analysis of a patient's WBC count.  This increase in the WBC count does not occur immediately following the administration of glucocorticoids in a patient, however this effect is known to manifest within 5-24 hours following administration and can persist during therapy.2,6 

    Why does the increase in WBC count manifest after 5-24 hours versus immediately?
    In order to understand why this biologic effect is not immediate, an understanding of the neutrophil's process for traveling along the endothelial lining of a blood vessel (i.e., within the marginal compartment) is needed.  Immature (bands) and mature (segmented) neutrophils both express a cell surface adhesion molecule called L-selectin (CD26L).10,11  This adhesion molecule is known to contribute to the formation of temporary carbohydrate-protein bonds on the surface of the endothelial cells lining the blood vessel wall.  The selectin adhesion molecules do not interact as tightly with the protein molecules on the endothelial surfaces and thus, allow for their ability to roll fast along the surface until alerted to transmigrate into the tissue to fight an infection.10,11  As such, L-selectins are known to undergo rapid turnover as they roll along the endothelial surface.12,13  In fact, the L-selectins are constantly being cleaved by membrane-associated cysteine metalloproteinase (also known as sheddase).12,13  The replacement of L-selectin to the surface of the cell membrane is dependent on the neutrophil's ability to undergo gene transcription to make more L-selectin that is then translated, packaged and prepared for transport to the cell surface to replace the shed L-selectin.6  If this does not occur, then the neutrophil's temporary or loosely bound carbohydrate-protein bonds are not sufficient to keep the neutrophil attached to the endothelial surface and thus, undergoes demargination into the circulatory compartment.6  It is the inhibition of gene transcription for L-selectin by glucocorticoids that results in the ability of the neutrophil to push newly formed L-selectin to the cell surface to replace the constant shedding of L-selectin by sheddase.6  The process of inhibiting gene transcription is not immediate and generally lags behind the initial pharmacologic effect of the medication.  The average time for this biologic effect to start to manifest on the WBC count has been shown to be between 5-24 hours.2,6  If glucocorticoids were to offer an immediate effect on neutrophil demargination they would likely activate sheddase, which has been shown to not be the case.14  Therefore, the surface cell adhesion protein, L-selectin is not being replaced and thus can no longer interact with the endothelium of the blood vessel.  

    Therefore, due to the small delay from the inhibition of gene transcription/translation for the production of new L-selectin, the increase WBC counts will not manifest for several hours post-administration of glucocorticoids.  While this may happen, the magnitude of the increase or effect seen may be influenced by the time the WBC is obtained from the patient in relation to the initial dosing of glucocorticoids, as well as when follow up labs are done.


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    2. 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.  
    3. 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.  
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    6. 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.  
    7. Liles WC, Dale DC, Klebanoff SJ.  Glucocorticoids inhibit apoptosis of human neutrophils.  Blood  1995;86:3181-8.  
    8. Cox G.  Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes.  J Immunol  1995;154:4719-25.  
    9. 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.  
    10. Tedder TF, Steeber DA, Chen A et al.  The selectins: vascular adhesion molecules.  FASEB J  1995;9:866-73.  
    11. Van Eeden S, Miyagashima R, Haley L et al.  L-selectin expression increases on peripheral blood polymorphonuclear leukocytes during active marrow release.  Am J Respir Crit Care Med  1995;151:500-7.  
    12. Preece G, Murphy G, Ager A.  Metalloproteinase-mediated regulation of L-selectin levels on leucocytes.  J Biol Chem  1996;271:11634-40.  
    13. Peschon JJ, Slack JL, Reddy P et al.  An essential role for ectodomain shedding in mammalian development.  Science 1998;282:1281-4.  
    14. Strausbaugh HJ, Rosen SD.  A potential role for annexin 1 as a physiologic mediator of glucocorticoid-induced L-selectin shedding from myeloid cells.  J Immunol  2001;166:6294-300.

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