INCREASED DEXAMETHASONE SENSITIVITY OF NEONATAL LEUKOCYTES - DIFFERENT MECHANISMS OF GLUCOCORTICOID INHIBITION OF T-CELL PROLIFERATION IN ADULT AND NEONATAL CELLS

Glucocorticoids (GC) are known to inhibit the proliferative response o f leukocytes after mitogenic activation. Until now, the effects of GC on the immune system have been studied predominantly in adults. Howeve r, GC are frequently administered to human fetuses and newborns for th e prevention and treatment of respiratory distress syndrome. The immun e system of human newborns is still a functionally immature system. Th erefore, we wondered whether the immaturity is also reflected by alter ed responses to hormonal signals such as glucocorticoids. We studied t he effects of the GC dexamethasone (DEX) on the proliferation of perip heral blood mononuclear cells and T cells in vitro after stimulation w ith phytohemagglutinin, anti-CD3, anti-CD3/anti-CD28 or anti-CD2/anti- CD28. Our data demonstrate that neonatal cells are much more sensitive to inhibition of the proliferative response by DEX than adult cells ( ED(50) 1 +/- 0.8 nM vs. 221 +/- 135 nM). This difference in sensitivit y is not related to differences in affinity and capacity of binding of [H-3] DEX. Moreover, we show that the mechanisms of GC inhibition dif fer between adult and neonatal cells. In adult cells, addition of inte rleukin (IL)-2 does not restore DEX inhibition of the proliferative re sponse. In contrast, the proliferative response of neonatal cells can be restored completely by the addition of IL-2. These data suggest tha t the primary target of GC in neonatal cells is inhibition of IL-2 pro duction. In adult cells, other mechanisms are responsible for inhibiti on of T cell proliferation.