white blood cell (WBC) count normally drawn from a patient is made up of a
number of different leukocytes which include neutrophils at 60-70%, lymphocytes
at 28%, monocytes at 5%, eosinophils at 2-4%, and basophils at 0.5% of the
total.1 When a WBC count is done on a patient, the lab value reflects 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 amount of leukocytes in the
total WBC count 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 in their appearance. 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 called to fight against.
This is normally seen or called a "left shift" in a WBC differential.2
As the immature neutrophils become activated or exposed to bacterial pathogens,
their nucleus will take on a segmented appearance. These and other
neutrophils can be found in several compartments within the body, but the two
compartments that relate to the importance of 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). All of this information is important for the proper
interpretation for the reasons that the WBC count has increased, especially
when glucocorticoids (e.g., dexamethasone, methylprednisolone, and prednisone)
are being given.
is well known that glucocorticoids (e.g., dexamethasone, methylprednisolone,
prednisone) cause increases in the WBC counts.2-4 Upon further evaluation
of the increased WBC count, it is the PMNs that contribute the most to the
increase. The causes for glucocorticoid induced increases in WBC counts
include demargination of neutrophils from the endothelial surface of blood
vessels, delayed transmigration of neutrophils into the tissue, delayed
apoptosis, and an increase in the release of neutrophils from the bone marrow.4-10
While all of these contribute to the increases in circulating neutrophils seen
on a WBC count, they do so at different degrees with demargination being the
predominate effect.4 Some studies have shown increases in WBC counts
greater than 20,000/mm3 that started as early as the first day and reached
maximum levels at approximately two weeks.3,6,11 The average increases in
WBC count have been reported to be approximately 4,000/mm3 in patients
taking 40-80 mg of oral prednisone, however there is a high degree of
variability that may, in part, be related to the dose of glucocorticoid.3,12
it is important to know the degree of increases in WBC counts, it is just as
important to be able to appropriately assess the WBC differential, so as to
avoid missing a treatable condition. The above increases in neutrophils
are made up by a small portion of immature (bands) WBC that predominately came
from the bone marrow. However, this contribution of bands does not
usually cause the same degree of a "left shift" that is normally
associated with presence of a bacterial infection.3 In addition,
glucocorticoid induced leukocytosis is generally not associated with increases
in temperature or worsening in the condition that is being appropriately treated.
Therefore, it is important for the clinician to put all of these factors in
context when assessing, monitoring and treating the patient's medical
- 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.
- Abramson N, Melton B. Leukocytosis: basic of clinical assessment. Am Fam Physician 2000;62:2053-60.
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.
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.
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.
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.
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.
- Liles WC, Dale DC, Klebanoff SJ. Glucocorticoids inhibit apoptosis of human neutrophils. Blood 1995;86:3181-8.
G. Glucocorticoid treatment inhibits apoptosis in human neutrophils.
Separation of survival and activation outcomes. J Immunol
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.
AS, Dale DC, Balow JE. Glucocorticoid therapy: mechanisms of action
and clinical considerations. Ann Intern Med 1976;84:304-15.
DC, Fauci AS, Guerry D IV et al. Comparison of agents producing a
neutrophilic leukocytosis in man. Hydrocortisone, prednisone,
endotoxin, and etiocholanolone. J Clin Invest 1975;56:808-13.