ENDOTOXIN PRETREATMENT OF HUMAN MONOCYTES ALTERS SUBSEQUENT ENDOTOXIN-TRIGGERED RELEASE OF INFLAMMATORY MEDIATORS
ENDOTOXIN PRETREATMENT OF HUMAN MONOCYTES ALTERS SUBSEQUENT ENDOTOXIN-TRIGGERED RELEASE OF INFLAMMATORY MEDIATORS
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DOI：
10.1097/00024382-199504000-00002
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发表时间：
1995-04-01
期刊：
影响因子：
3.1
通讯作者：
WEST, MA
中科院分区：
文献类型：
--
作者：
SEATTER, SC;LI, MH;WEST, MA
在创伤或脓毒症中，单核细胞和巨噬细胞释放介质，如肿瘤坏死因子（TNF）、白细胞介素-1（IL-1）、白细胞介素-6（IL-6）和前列腺素E（2）（PGE（2））。虽然患者可能暴露于一种以上的刺激，但重复内毒素（LPS）刺激对人单核细胞的影响特征不佳。从健康志愿者中获得的人外周血单核细胞用内毒素（LPS（1））预处理24 h。然后用不同浓度的第二种激活LPS刺激物（LPS（2））再刺激培养物24 h，并测量上清液介质（TNF、IL-1、IL-6和PGE（2））。将正常单核细胞供体的血清细胞因子水平与其单核细胞在体外的基础和LPS刺激的细胞因子释放进行比较。LPS（2）在无LPS（1）预处理的情况下以剂量依赖性方式增加所有介质。LPS（1）显著增加LPS（2）触发的单核细胞分泌IL-1、IL-6和PGE（2），但抑制TNF的释放。细胞相关的TNF和IL-1也被抑制和增强与各自的细胞因子的上清液水平平行。血清细胞因子水平较低，表现出广泛的变化，并与体外LPS触发的细胞因子的生产相关性较差。内毒素预处理对人单核细胞介质产生的调节差异单核细胞的激发性体外测试可以识别先前的LPS暴露，并且可能比血清细胞因子测量更有用。
In trauma or sepsis, monocytes and macrophages release mediators such as tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), and prostaglandin E(2) (PGE(2)). Although patients may be exposed to more than one stimulus, the effect of repetitive endotoxin (LPS) stimulation on human monocytes is poorly characterized. Human peripheral blood monocytes obtained from healthy volunteers were pretreated with endotoxin (LPS(1)) for 24 h. Cultures were then restimulated for 24 h with a second, activating LPS stimulus (LPS(2)) at various concentrations and supernatant mediators (TNF, IL-1, IL-6, and PGE(2)) measured. Serum cytokine levels of normal monocyte donors were compared to basal and LPS-stimulated cytokine release of their monocytes in vitro. LPS(2) increased all mediators in a dose-dependent manner in the absence of LPS(1) pretreatment. LPS(1) significantly increased LPS(2)-triggered monocyte secretion of IL-1, IL-6, and PGE(2), but inhibited TNF release. Cell-associated TNF and IL-1 were also inhibited and enhanced in parallel with supernatant levels of the respective cytokines. Serum cytokine levels were low, showed wide variation, and correlated poorly with in vitro LPS-triggered cytokine production. Human monocyte mediator production is differentially regulated by endotoxin pretreatment. Provocative in vitro testing of monocytes could identify prior LPS exposure and may be more useful than serum cytokine measurements.