Document Detail


Increased dexamethasone sensitivity of neonatal leukocytes: different mechanisms of glucocorticoid inhibition of T cell proliferation in adult and neonatal cells.
MedLine Citation:
PMID:  7774638     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 +/- 0.8 nM vs. 221 +/- 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 (IL)-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.
Authors:
A Kavelaars; J Zijlstra; J M Bakker; E P Van Rees; G H Visser; B J Zegers; C J Heijnen
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of immunology     Volume:  25     ISSN:  0014-2980     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  1995 May 
Date Detail:
Created Date:  1995-07-13     Completed Date:  1995-07-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  1346-51     Citation Subset:  IM    
Affiliation:
Department of Immunology, University Hospital for Children and Youth Het Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aging / immunology
Antibodies, Monoclonal / pharmacology
Antigens, CD28 / immunology
Antigens, CD45 / analysis
Cell Division / drug effects
Cells, Cultured
Dexamethasone / adverse effects,  pharmacology*
Fetal Blood / cytology
Gene Expression Regulation / drug effects
Humans
Immunosuppressive Agents / adverse effects,  pharmacology*
Infant, Newborn / immunology*
Interleukin-2 / pharmacology
Leukocytes, Mononuclear / drug effects,  immunology
Lymphocyte Activation / drug effects*
Muromonab-CD3 / pharmacology
Phytohemagglutinins / pharmacology
Receptors, Interleukin-2 / biosynthesis,  genetics
T-Lymphocytes / drug effects*,  immunology
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD28; 0/Immunosuppressive Agents; 0/Interleukin-2; 0/Muromonab-CD3; 0/Phytohemagglutinins; 0/Receptors, Interleukin-2; 50-02-2/Dexamethasone; EC 3.1.3.48/Antigens, CD45

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