Vancomycin down-regulates lipopolysaccharide-induced tumour necrosis factor alpha (TNF alpha) production and TNF alpha-mRNA accumulation in human blood monocytes

Vancomycin down-regulates lipopolysaccharide-induced tumour necrosis factor alpha (TNF alpha) production and TNF alpha-mRNA accumulation in human blood monocytes
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DOI:
10.1016/s0162-3109(96)00156-7
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发表时间:
1997-01-01
期刊:
IMMUNOPHARMACOLOGY
影响因子:
--
通讯作者:
Zembala, M
Zembala, M
中科院分区:
其他
文献类型:
--
作者:
Siedlar, M;Szczepanik, A;Zembala, M

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细胞因子在导致感染性休克的病理事件级联反应中起重要作用。单核细胞/巨噬细胞在细菌片段刺激下产生的TNF α可能有助于诱导这种细胞因子级联反应。此外,用于抗菌治疗的抗生素可能由于大量细菌杀伤和单核/巨噬细胞暴露于细菌细胞成分而导致TNF α产生增加。为了研究万古霉素对TNF α产生的影响,我们使用了lps刺激单核细胞的体外模型。用LPS检测单核细胞培养上清中TNF α蛋白水平或TNF生物活性。万古霉素呈剂量依赖性下调TNF α的产生。万古霉素还能抑制lps刺激的单核细胞中TNF α - mrna的积累,这是通过细胞悬液中的荧光原位杂交(FISH)来评估的。lps刺激的单核细胞TNF α产生下调可能表明抑制这种细胞因子的释放是万古霉素治疗脓毒症的重要作用之一。
The cytokines play an important role in the cascade of the pathological events leading to septic shock. The TNF alpha produced by monocytes/macrophages upon stimulation with bacterial fragments may contribute to induction of this cytokine cascade. Moreover, the antibiotics used for antimicrobial therapy may cause the increase of TNF alpha production due to massive bacterial killing and exposure of monocytes/macrophages to bacterial cell constituents. To investigate the effect of Vancomycin on TNF alpha production, an in vitro model of LPS-stimulated monocytes was used. The level of TNF alpha protein or TNF biological activity were tested in the culture supernatants of monocytes with LPS. Vancomycin down-regulated, in dose-dependent manner, the TNF alpha production. Vancomycin also inhibited TNF alpha-mRNA accumulation in LPS-stimulated monocytes, as assessed by fluorescence in situ hybridization (FISH) in cell suspension. The down-regulation of TNF alpha production in LPS-stimulated monocytes may indicate that inhibition of this cytokine release is one of the important therapeutic effects of Vancomycin in sepsis.