Increased dexamethasone sensitivity of neonatal leukocytes: different mechanisms of glucocorticoid inhibition of T cell proliferation in adult and neonatal cells

✍ Scribed by Annemieke Kavelaars; Jitske Zijlstra; Joost M. Bakker; Emmelien P. Van Rees; Gerard H. A. Visser; Ben J. M. Zegers; Cobi J. Heijnen

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 644 KB
• Volume: 25
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830250532

✦ Synopsis

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 of leukocytes after mitogenic activation. Until now, the effects of GC on the immune system have been studied predominantly in adults. However, GC are frequently administered to human fetuses and newborns for the prevention and treatment of respiratory distress syndrome. The immune system of human newborns is still a functionally immature system. Therefore, we wondered whether the immaturity is also reflected by altered responses to hormonal signals such as glucocorticoids. We studied the effects of the GC dexamethasone (DEX) on the proliferation of peripheral blood mononuclear cells and T cells in vitro after stimulation with 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 (ED50 1 k 0.8 nM vs.

221 k 135 nM).This difference in sensitivity is not related to differences in affinity and capacity of binding of [3H] DEX. Moreover, we show that the mechanisms of GC inhibition differ between adult and neonatal cells. In adult cells, addition of interleukin (1L)-2 does not restore DEX inhibition of the proliferative response. In contrast, the proliferative response of neonatal cells can be restored completely by the addition of IL-2.These data suggest that the primary target of GC in neonatal cells is inhibition of IL-2 production. In adult cells, other mechanisms are responsible for inhibition of T cell proliferation.