Linezolid, vancomycin and daptomycin modulate cytokine production, Toll-like receptors and phagocytosis in a human in vitro model of sepsis.
Linezolid, vancomycin and daptomycin modulate cytokine production, Toll-like receptors and phagocytosis in a human in vitro model of sepsis.
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DOI：
10.1038/ja.2015.18
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发表时间：
2015-08
期刊：
影响因子：
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通讯作者：
Baumgarten G
中科院分区：
文献类型：
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作者：
Bode C;Muenster S;Diedrich B;Jahnert S;Weisheit C;Steinhagen F;Boehm O;Hoeft A;Meyer R;Baumgarten G
常规抗生素表现出有益于脓毒症治疗的免疫调节特性。抗生素耐药性革兰氏阳性菌已成为脓毒症治疗中的一个问题，导致增加使用最后手段抗生素;例如利奈唑胺（LIN）、万古霉素（货车）和达托霉素（DAP）。由于这些抗生素在治疗脓毒症中的免疫调节特性尚不清楚，因此本研究检查了货车、LIN和DAP在体外脓毒症样条件下对免疫应答的影响。将脂多糖（LPS）活化的THP-1单核细胞与LIN、货车或DAP孵育。检测细胞因子（TNFα、IL-1β、IL-6、IL-10）和Toll样受体（TLR 1、2、4、6、7和9）的基因表达，并在与E.杆菌抗生素差异调制的基因表达的研究细胞因子。而LIN和货车上调所有TLR的表达，DAP下调TLR 1，TLR 2和TLR 6的mRNA水平，这些分子识别来自革兰氏阳性菌的病原体相关分子模式。此外，LIN抑制单核细胞的吞噬活性，而货车促进单核细胞的吞噬活性。我们的研究结果表明，LIN和货车具有促炎特性，而DAP可能降低脓毒症中对革兰氏阳性菌的免疫反应。此外，货车可能通过增加E.杆菌
Conventional antibiotics exhibit immunomodulatory properties beneficial in the treatment of sepsis. Antibiotic-resistant Gram-positive bacteria have become a problem in sepsis therapy, giving rise to increased use of last-resort antibiotics; for example, linezolid (LIN), vancomycin (VAN) and daptomycin (DAP). As the immunomodulatory properties of these antibiotics in treating sepsis are unknown, this study examined the effect of VAN, LIN and DAP on the immune response under sepsis-like conditions in vitro. Lipopolysaccharide (LPS)-activated THP-1 monocytes were incubated with LIN, VAN or DAP. Gene expression of cytokines (TNFα, IL-1β, IL-6, IL-10) and Toll-like receptors (TLR1, 2, 4, 6, 7 and 9) was monitored and phagocytosis was determined following coincubation with E. coli. The antibiotics differentially modulated the gene expression of the investigated cytokines. While LIN and VAN upregulated the expression of all TLRs, DAP downregulated mRNA levels of TLR1, TLR2 and TLR6, which recognize pathogen-associated molecular patterns from Gram-positive bacteria. In addition, LIN inhibited, whereas VAN promoted the phagocytic activity of monocytes. Our results suggest that LIN and VAN possess pro-inflammatory properties, whereas DAP might reduce the immune response to Gram-positive bacteria in sepsis. Furthermore, VAN might be beneficial in the prevention of Gram-negative infections by increasing the phagocytosis of E. coli.