Neonatal dexamethasone treatment increases susceptibility to experimental autoimmune disease in adult rats

被引:63
作者
Bakker, JM
Kavelaars, A
Kamphuis, PJGH
Cobelens, PM
van Vugt, HH
van Bel, F
Heijnen, CJ
机构
[1] Univ Utrecht, Wilhelmina Childrens Hosp, Med Ctr, Dept Pediat Immunol, NL-3584 EA Utrecht, Netherlands
[2] Univ Utrecht, Wilhelmina Childrens Hosp, Med Ctr, Dept Neonatol, NL-3584 EA Utrecht, Netherlands
[3] Univ Utrecht, Rudolf Magnus Inst, Utrecht, Netherlands
关键词
D O I
10.4049/jimmunol.165.10.5932
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Major concern has emerged about the possible long term adverse effects of glucocorticoid treatment, which is frequently used for the prevention of chronic lung disease in preterm infants. Here we show that neonatal glucocorticoid treatment of rats increases the severity (p less than or equal to 0.01) and incidence (p less than or equal to 0.01) of the inflammatory autoimmune disease experimental autoimmune encephalomyelitis in adult life, In search of possible mechanisms responsible for the increased susceptibility to experimental autoimmune encephalomyelitis, we investigated the reactivity of the hypothalamo-pituitary-adrenal asis and of immune tells in adult rats after neonatal glucocorticoid treatment. We observed that neonatal glucocorticoid treatment reduces the corticosterone response after an LPS challenge in adult rats (p less than or equal to 0.001), Interestingly, LPS-stimulated macrophages of glucocorticoid-treated rats produce less TNF-alpha and IL-1 beta in adult life than control rats (p less than or equal to 0.05), In addition, splenocytes obtained from adult rats express increased mRNA levels of the proinflammatory cytokines IFN-gamma (p < 0.01) and TNF-<beta> (p < 0.05) after neonatal glucocorticoid treatment. Apparently, neonatal glucocorticoid treatment has permanent programming effects on endocrine as well as immune functioning in adult life, In view of the frequent clinical application of glucocorticoids to preterm infants, our data demonstrate that neonatal glucocorticoid treatment may be a risk factor for the development of (auto)immune disease in man.
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页码:5932 / 5937
页数:6
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