Glucocorticoids dose-dependently increase plasma levels of granulocyte colony stimulating factor in man.
Glucocorticoids increase neutrophil counts by decreasing the margination of neutrophils and mobilizing neutrophils from the bone marrow pool. The mechanisms for these effects however are not fully elucidated, but it has been demonstrated that dexamethasone enhances release of colony stimulating factor (G-CSF) in-vitro. We therefore hypothesized, that dexamethasone may increase plasma levels of G-CSF. A double blind, randomized, placebo-controlled, three-way cross-over trial was conducted in nine healthy men. Every subject received four identical infusions of saline, 0.04 mg/kg or 1.0 mg/kg dexamethasone during three observation periods of 48 hours each. The low dose of dexamethasone increased G-CSF levels from a baseline of 15.5 ng/L (CI: 10.6-20.4) by 240% (CI: 115-366%) at 24 hours. The high dexamethasone dose increased G-CSF levels from a baseline of 12.3 ng/L (CI: 9.7-14.9) by 871% (CI: 592-1149%) at 24 hours (p=0.008 for all comparisons). No further increase was observed at 48 hours but the effect was less pronounced (p<0.008 and p=0.08 for the high and the low dose of dexamethasone, respectively). Granulocyte-macrophage-CSF (GM-CSF) levels were below the assay's detection limit of 0.36 ng/L in all subjects. In conclusion, dexamethasone dose dependently increases G-CSF levels in healthy men, an effect which may account for some of its effects on neutrophils.
Jilma
B
B
Department of Clinical Pharmacology, University Hospital of Vienna, Wien, Austria.
Stohlawetz
P
P
Pernerstorfer
T
T
Eichler
H G
HG
Müllner
C
C
Kapiotis
S
S
D000328:Adult; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood*; D006801:Humans; D008297:Male; D013997:Time Factors
D005938:Glucocorticoids; D016179:Granulocyte Colony-Stimulating Factor; D003907:Dexamethasone