Background

Endotoxemia induces pronounced changes in leukocyte count and enhances the release of many cytokines. However, the molecular regulation of this cytokine release is poorly characterized in humans.

Methods

The time course of mRNA expression of 24 cytokines in circulating leukocytes was studied in a wellstandardized model of human endotoxemia (2 ng/kg). Real-time polymerase chain reaction (RT-PCR) was used to quantify the lipopolysaccharide (LPS)-inducible mRNA levels of leukocytes from 16 healthy volunteers in a randomized, placebo-controlled trial.

Results

Baseline mRNA levels of interleukins including IL-1α, IL-3, IL-5, IL-6, IL-12p40, IL-13, IL-15, IL-17, granulocyte colony-stimulating factor (G-CSF) and granulocyte monocyte CSF (GM-CSF) were below detectable levels in normal blood of the healthy participants. After 2 h, LPS infusion increased median mRNA levels of IL-1α by >1100-fold and IL-1β and IL-8 by 33-fold and 46-fold, respectively. In contrast, levels of tumor necrosis factor (TNF-α) and IL-10 mRNA increased by only 7-fold, whereas changes in mRNA expression of other cytokines showed either a more than two fold increase or were undetectable. In vitro incubation of whole blood with 50 pg/mL LPS for 2 h enhanced transcription levels of IL-1α mRNA by >10,000-fold, IL-6 and IL-12p40 by >1000-fold, IL-1α by 400-fold, TNF-α by 100-fold, IL-8, IL-18, interferon γ (IFN-γ) and G-CSF by >10-25-fold, and IL-10, IL-12p35, TNF-β, and IL-13 by 10-25-fold.

Conclusion

Only half of the 24 evaluated cytokines were expressed at the mRNA level in circulating leukocytes under basal conditions and after an LPS challenge. Only IL-1α, IL-1β, IL-10, IL-8, and TNF-α were upregulated in the circulating leukocytes, whereas several other cytokines (including IL-6 and G-CSF), were expressed on the mRNA level following in vitro incubation of blood with LPS. In addition, IL-1α and IL-1β might be potential diagnostic targets in inflammatory diseases.

中文翻译：

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人内毒素血症期间循环白细胞中细胞因子mRNA的上调。

背景

内毒素血症可引起白细胞计数的明显改变，并增强许多细胞因子的释放。但是，这种细胞因子释放的分子调控在人类中的特征较差。

方法

在人内毒素血症（2 ng / kg）的标准化模型中研究了循环白细胞中24种细胞因子的mRNA表达的时程。在一项随机，安慰剂对照试验中，实时聚合酶链反应（RT-PCR）用于量化来自16名健康志愿者的白细胞脂多糖（LPS）诱导的白细胞mRNA水平。

结果

IL-1α，IL-3，IL-5，IL-6，IL-12p40，IL-13，IL-15，IL-17，粒细胞集落刺激因子（G-CSF）和粒细胞的白介素的基线mRNA水平健康参与者正常血液中的单核细胞CSF（GM-CSF）低于可检测水平。2小时后，LPS输注可使IL-1α的中值mRNA水平分别增加1100倍和IL-1β和IL-8的33倍和46倍。相比之下，肿瘤坏死因子（TNF-α）和IL-10 mRNA的水平仅增加了7倍，而其他细胞因子的mRNA表达的变化则显示出增加了两倍以上或无法检测到。体外 将全血与50 pg / mL LPS孵育2小时可提高IL-1αmRNA的转录水平> 10,000倍，IL-6和IL-12p40的转录水平> 1000倍，IL-1α的400倍，TNF-α α乘以100倍，IL-8，IL-18，干扰素γ（IFN-γ）和G-CSF乘以10-25倍以上，IL-10，IL-12p35，TNF-β和IL-13减少10-25倍

结论

在基础条件下和LPS攻击后，在24种评估的细胞因子中，只有一半在循环白细胞的mRNA水平上表达。在循环白细胞中仅IL-1α，IL-1β，IL-10，IL-8和TNF-α被上调，而在随后的mRNA水平上表达了其他几种细胞因子（包括IL-6和G-CSF）。用LPS在体外培养血液。此外，IL-1α和IL-1β可能是炎性疾病的潜在诊断目标。