Differential effects of glucocorticoids on colony stimulating factors produced by neonatal mononuclear cells

Abstract

The purpose of this study was to examine the effect of dexamethasone (DEX) on the production of granulocyte and granulocyte-macrophage colony stimulating factors (G-CSF and GM-CSF) by neonatal mononuclear cells. Mononuclear cells were isolated from umbilical cord blood and cultured with either phorbol myristate acetate/phytohemagglutinin (PMA/PHA) or Candida albicans with or without DEX (10-8-10-6 M) for 48 h. Cell supernatants were assayed for G-CSF and GM-CSF by ELISA. Mononuclear cells from term and preterm infants responded to PMA/PHA stimulation with a significant increase in G-CSF production over baseline levels. The PMA/PHA-induced increase in G- CSF production was markedly augmented by the addition of DEX to cell cultures. DEX augmented production of G-CSF was significantly less in mononuclear cells from preterm infants. Similarly, production of G-CSF was significantly less by mononuclear cells from infants with acute physiology scores of ≥10, as judged by the Score for Acute Neonatal Physiology. In contrast, DEX significantly inhibited PMA/PHA-induced GM-CSF production. Although C. albicans induced mononuclear cells to produce G-CSF, DEX did not significantly augment this production. No significant effect of DEX on C. albicans induced GM-CSF production was observed. The data show DEX induced differential regulation of infant peripheral blood mononuclear cell production of G-CSF and GM-CSF. These results suggest that glucocorticoids may enhance certain aspects of host immune function in addition to their well-documented immunosuppressive effects. Further, the neutrophilia observed in DEX-treated infants may be due to enhanced G-CSF production.