Adrenalectomy enhances pro-inflammatory cytokines gene expression, in the spleen, pituitary and brain of mice in response to lipopolysaccharide
Adrenalectomy enhances pro-inflammatory cytokines gene expression, in the spleen, pituitary and brain of mice in response to lipopolysaccharide
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DOI：
10.1016/0169-328x(95)00242-k
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发表时间：
1996-02-01
期刊：
影响因子：
--
通讯作者：
Dantzer, R
中科院分区：
文献类型：
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作者：
Goujon, E;Parnet, P;Dantzer, R
为了评估内源性糖皮质激素对脑中细胞因子表达的可能影响，肾上腺切除小鼠和假手术小鼠注射生理盐水或脂多糖，（LPS，10 μ g/小鼠，皮下）和IL-1 α、IL-1 β、IL-1 ra、IL-6和肿瘤坏死因子-α的转录物水平用半定量逆转录聚合酶链反应（RT-PCR）测定给药后2 h脾脏、垂体、下丘脑、海马和纹状体中TNF α的含量。在给予LPS或盐水后处死的小鼠的血浆和组织中通过ELISA测量IL-1 β的水平。LPS诱导的促炎细胞因子的表达在mRNA水平在所有组织的研究，除了在海马中的TNF α。通过切除脾脏中的肾上腺（用于IL-1 α和IL-1 ra）、垂体（用于IL-1 ra以外的细胞因子）、下丘脑（用于所有细胞因子）、海马（用于TNF α以外的细胞因子）和纹状体（用于IL-1 α和IL-6），增强了该效应。在盐水处理的小鼠中，肾上腺切除增加了下丘脑中IL-1 α和IL-1 β的基因表达以及海马和纹状体中IL-1 α的基因表达。LPS增加IL-1 β的血浆和组织水平，如通过ELISA测定的，并且这种作用通过肾上腺切除术在血浆和组织中而不是脾中增强。这些结果可以解释为表明，内源性糖皮质激素调节宿主的神经成分的感染和炎症反应，通过抑制细胞因子在外周器官和大脑的表达。
To assess the possible influence of endogenous glucocorticoids on cytokine expression in the brain, adrenalectomized mice and sham operated mice were injected with saline or lipopolysaccharide (LPS, 10 mu g/mouse, subcutaneously) and the levels of transcripts for IL-1 alpha, IL-1 beta, IL-1ra, IL-6 and tumor necrosis factor-alpha (TNF alpha) were determined 2 h after treatment in the spleen, pituitary, hypothalamus, hippocampus and striatum, using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Levels of IL-1 beta were measured by ELISA in plasma and tissues of mice sacrificed after the administration of LPS or saline. LPS induced the expression of pro-inflammatory cytokines at the mRNA level in all tissues under investigation, except for TNF alpha in the hippocampus. This effect was potentiated by adrenalectomy in the spleen for IL-1 alpha and IL-1ra, the pituitary for cytokines other than IL-1ra, the hypothalamus for all cytokines, the hippocampus for cytokines other than TNF alpha, and the striatum for IL-1 alpha and IL-6. In saline-treated mice, adrenalectomy increased IL-1 alpha and IL-1 beta gene expression in the hypothalamus and IL-1 alpha gene expression in the hippocampus and striatum. LPS increased plasma and tissue levels of IL-1 beta, as determined by ELISA, and this effect was potentiated by adrenalectomy in plasma and tissues other than the spleen. These results can be interpreted to suggest that endogenous glucocorticoids regulate the neural components of the host response to infection and inflammation by inhibiting cytokine expression in peripheral organs and the brain.