Methicillin-resistant Staphylococcus aureus-induced thrombo-inflammatory response is reduced with timely antibiotic administration.
Methicillin-resistant Staphylococcus aureus-induced thrombo-inflammatory response is reduced with timely antibiotic administration.
复制标题
DOI：
10.1160/th12-08-0543
复制
发表时间：
2013-04
影响因子：
6.7
通讯作者：
Rondina MT
中科院分区：
文献类型：
--
作者：
Franks Z;Campbell RA;Vieira de Abreu A;Holloway JT;Marvin JE;Kraemer BF;Zimmerman GA;Weyrich AS;Rondina MT
耐甲氧西林金黄色葡萄球菌 (MRSA) 会诱发促血栓形成和促炎症环境。尽管在 MRSA 脓毒症中及时使用抗生素可能会通过阻止细菌生长来改善预后，但抗生素对减轻有害的血栓炎症细胞反应的作用仍有待探索。使用新开发的人类全血模型和 MRSA 感染的体内小鼠模型，我们研究了抗生素如何抑制 MRSA 诱导的血栓炎症途径。人类全血接种了 MRSA。在存在或不存在利奈唑胺和万古霉素的情况下测量凝血酶的生成和炎症细胞因子的合成。 C57BL/6小鼠注射MRSA并检查万古霉素给药的效果。 MRSA 以时间和浓度依赖性方式加速凝血酶的产生，并诱导细胞因子的释放，包括白细胞介素 (IL)-6、IL-8 和单核细胞趋化蛋白 (MCP)-1。凝血酶生成和炎症反应的增加分别通过组织因子和细胞因子的合成以及微粒的释放来介导。早期施用抗生素可恢复正常的凝血酶生成模式并显着减少细胞因子的合成。相反，当延迟抗生素给药时，凝血酶的生成和细胞因子的合成并未显着减少。在感染 MRSA 的小鼠中，早期施用抗生素会减少凝血酶抗凝血酶复合物和细胞因子合成，而延迟施用抗生素则不会。这些数据提供了新的机制证据，证明了及时施用抗生素在感染综合征中的重要性。
Methicillin-resistant Staphylococcus aureus (MRSA) induces a pro-thrombotic and pro-inflammatory milieu. Although timely antibiotic administration in MRSA sepsis may improve outcomes by arresting bacterial growth, the effects of antibiotics on mitigating injurious thrombo-inflammatory cellular responses remains unexplored. Using a newly developed human whole blood model and an in vivo mouse model of MRSA infection, we examined how antibiotics inhibit MRSA induced thrombo-inflammatory pathways. Human whole blood was inoculated with MRSA. Thrombin generation and inflammatory cytokine synthesis was measured in the presence or absence of linezolid and vancomycin. C57BL/6 mice were injected with MRSA and the effect of vancomycin administration was examined. MRSA accelerated thrombin generation in a time- and concentration-dependent manner and induced the release of cytokines, including interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1. The increase in thrombin generation and inflammatory responses was mediated through the synthesis of tissue factor and cytokines, respectively, and the release of microparticles. The early administration of antibiotics restored normal thrombin generation patterns and significantly reduced the synthesis of cytokines. In contrast, when antibiotic administration was delayed, thrombin generation and cytokine synthesis were not significantly reduced. In mice infected with MRSA, early antibiotic administration reduced thrombin anti-thrombin complexes and cytokine synthesis, whereas delayed antibiotic administration did not. These data provide novel mechanistic evidence of the importance of prompt antibiotic administration in infectious syndromes.