105 glucocorticoid sensitivity of human neonatal leukocytes

Glucocorticoids (GC) are widely used as immunosuppressive and antiinflammatory drugs. They are known to inhibit the proliferative response of leukocytes after activation with mitogen, possibly by interfering with the interleukin-2 (IL-2) mRNA synthesis. Apart from IL-2 mRNA, GC also inhibit the transcription of genes encoding for IL-1 and IL-6. Until now, the effects of GC have predominantly been studied in adults. Therefore we studied the in vitro effects of the GC dexamethasone on the proliferative capacity of T cells in 15 human newborns. Our data show that neonatal leukocytes are more sensitive for inhibition of the proliferative response by dexamethasone than adult cells (EC 50 neonatal cells: 10−9 M; adults 3.10−8M p<0.01). This difference in sensitivity is not related to differences in GC receptor expression in neonatal and adult cells. Dexamethasone inhibits the expression of the IL-2 receptor on neonatal cells to a larger extent than on adult cells (70% versus 25% inhibition). However, this difference can not explain the difference in sensitivity between adult and neonatal cells. We show that the increased sensitivity of neonatal cells for GC is due to their diminished capacity to produce IL-2. Addition of interleukin-2 can restore the proliferative capacity after dexamethasone inhibition of neonatal cell proliferation.