Differential regulation of lipopolysaccharide‐induced interleukin 1 and tumor necrosis factor synthesis: effects of endogenous and exogenous glucocorticoids and the role of the pituitary‐adrenal axis

Differential regulation of lipopolysaccharide‐induced interleukin 1 and tumor necrosis factor synthesis: effects of endogenous and exogenous glucocorticoids and the role of the pituitary‐adrenal axis
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脂多糖诱导的白细胞介素1和肿瘤坏死因子合成的差异调节:内源性和外源性糖皮质激素的作用以及垂体-肾上腺轴的作用

DOI:
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发表时间:
1989
影响因子:
5.4
通讯作者:
Larry D. Butter
Larry D. Butter
中科院分区:
医学3区
文献类型:
--
作者:
S. Zuckerman;J. Shellhaas;Larry D. Butter

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腹腔注射亚致死剂量的脂多糖(LPS)到小鼠导致肿瘤坏死因子(TNF)在血清中的外观在45分钟内。最大血清TNF检测到1小时,3-4小时TNF水平不再显着高于基线。在4 h时给小鼠注射额外剂量的LPS导致血清TNF没有进一步增加。TNF出现的体内动力学与体外研究相关,其中LPS刺激后30分钟在小鼠腹腔巨噬细胞中检测到TNF mRNA。在LPS刺激前用地塞米松(3 mg/kg)处理的小鼠中未检测到血清TNF的增加。TNF的降低与显著量的内源性血清皮质酮的出现相关,其在3 h时达到最大。在肾上腺切除或垂体切除小鼠的研究中获得了内源性类固醇在调节血清TNF水平中作用的进一步证据。与假手术动物相比,在肾上腺切除或hypohysectomized小鼠中,血清TNF水平在LPS刺激后5 h保持升高。与TNF的一过性升高相反,血清IL 1在LPS注射后4 h达到最大值,并在24 h保持升高。人外周血单核细胞和人脐带静脉内皮细胞原代培养物的体外研究表明,10 - 1 M地塞米松可使LPS诱导的单核细胞IL 1水平降低约5倍,而地塞米松对内皮细胞IL 1的影响极小。因此,体外数据表明,LPS休克期间IL 1水平升高的维持与内源性皮质类固醇的出现一致,这与单核细胞-巨噬细胞和包括内皮细胞在内的非骨髓细胞群合成IL 1有关。
Intraperitoneal injection of a sublethal dose of lipopolysaccharide (LPS) into mice resulted in the appearance of tumor necrosis factor (TNF) in the serum within 45 min. Maximal serum TNF was detected by 1 h, and by 3–4 h TNF levels were no longer significantly above baseline. Injection of mice with an additional dose of LPS at 4 h resulted in no further increase in serum TNF. The in vivo kinetics of TNF appearance correlated with in vitro studies in which TNF mRNA was detected in murine peritoneal macrophages 30 min after LPS stimulation. The increase in serum TNF was not detected in mice treated with dexamethasone, 3 mg/kg, prior to LPS stimulation. The decrease in TNF correlated with the appearance of significant amounts of endogenous serum corticosterone which were maximal by 3 h. Further evidence for the role of endogenous steroids in the modulation of serum TNF levels was obtained in studies with adrenalectomized or hypophysectomized mice. Compared to sham‐operated animals, serum TNF levels remain elevated 5 h post LPS stimulation in adrenalectomized or hypohysectomized mice. In contrast with the transient increase in TNF, serum IL 1 was maximal 4 h post LPS injection and remained elevated at 24 h. In vitro studies with primary cultures of human peripheral blood monocytes and human umbilical cord vein endothelial cells demonstrated that LPS‐induced mono‐cyte IL 1 levels were reduced approximately 5‐fold by 10‐1 M dexamethasone while dexamethasone had only minimal effects on endothelial cell IL 1. Therefore, the in vitro data would suggest that the maintenance of elevated IL 1 levels coincident with the appearance of endogenous corticosteroids during LPS shock is related to the synthesis of IL 1 by both monocyte‐macrophages and non‐myeloid cell populations including endothelial cells.
DOI: 10.4049/jimmunol.136.1.186
发表时间: 1986-01
影响因子: 4.4
作者:
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通讯作者: S. Kunkel;S. Chensue;S. Phan
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DOI: --
发表时间: 1987
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Fuhlbrigge,RC;Chaplin,DD;Kiely,JM;Unanue,ER
通讯作者: Unanue,ER
DOI: 10.1056/nejm198806093182301
发表时间: 1988-06-09
影响因子: 158.5
作者:
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DOI: 10.1172/jci113431
发表时间: 1988-04-01
影响因子: 15.9
作者:
OKUSAWA, S;GELFAND, JA;DINARELLO, CA
通讯作者: DINARELLO, CA
皮质类固醇抑制小鼠巨噬细胞 Ia 表达和白细胞介素 1 产生。
DOI: --
发表时间: 1982
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
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通讯作者: Unanue,ER