GLUCOCORTICOIDS DOSE-DEPENDENTLY INCREASE PLASMA-LEVELS OF GRANULOCYTE-COLONY-STIMULATING FACTOR IN MAN

Glucocorticoids increase neutrophil counts by decreasing the marginati on of neutrophils and mobilizing neutrophils from the bone marrow pool . The mechanisms for these effects however are not fully elucidated, b ut it has been demonstrated that dexamethasone enhances release of col ony stimulating factor (G-CSF) in-vitro. We therefore hypothesized, th at dexamethasone may increase plasma levels of G-CSF. A double blind, randomized, placebo-controlled, three-way cross-over trial was conduct ed in nine healthy men. Every subject received four identical infusion s of saline, 0.04 mg/kg or 1.0 mg/kg dexamethasone during three observ ation periods of 48 hours each. The low dose of dexamethasone increase d G-CSF levels from a baseline of 15.5 ng/L (CI: 10.6-20.4) by 240% (C I: 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: 592-11 49%) at 24 hours (p=0.008 for all comparisons). No further increase wa s 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 det ection limit of 0.36 ng/L in all subjects. In conclusion, dexamethason e dose dependently increases G-CSF levels in healthy men, an effect wh ich may account for some of its effects on neutrophils.