Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia.
Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia.
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Linezolid在后炎后社区中具有独特的免疫调节作用，获得了MRSA肺炎。
DOI：
10.1371/journal.pone.0114574
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Standiford TJ
中科院分区：
文献类型：
--
作者：
Bhan U;Podsiad AB;Kovach MA;Ballinger MN;Keshamouni V;Standiford TJ
流感后肺炎是死亡和发病的主要原因，当细菌感染继发于多药耐药(MDR)病原体时，死亡率接近60%。金黄色葡萄球菌，特别是社区获得性耐甲氧西林金黄色葡萄球菌(CMRSA)已成为流感后肺炎的主要原因。利奈唑胺(LZD)预防小鼠流感后细菌性肺炎模型的急性肺损伤小鼠感染HINI流感病毒株后，在第7天给予cMRSA攻击，在细菌攻击后6小时给予抗生素(LZD或VANCO)或赋形剂治疗，并于24小时采集肺和支气管肺泡灌洗液(BAL)，进行细菌清除、炎症细胞内流、细胞因子/趋化因子分析和肺损伤评估。与对照组(没有抗生素)相比，在细菌攻击后24小时，接受LZD或Vanco治疗的小鼠肺部细菌负荷较低，且没有全身扩散。与VANCO组相比，LZD组大鼠肺泡灌洗液中中性粒细胞数量显著减少(9×10~3比2.3×10~4，p<；0.01)，这与肺泡灌洗液中趋化趋化因子KC、MIP-2、干扰素-γ、肿瘤坏死因子-α和IL-1β水平降低有关。有趣的是，LZD治疗也保护小鼠免受肺损伤，这是通过与Vanco治疗相比，H1N1和cMRSA治疗后BAL中的白蛋白浓度来评估的。此外，LZD治疗与肺内PVL毒素水平显著降低有关。利奈唑胺在病毒后cMRSA肺炎小鼠模型中对宿主炎症反应和肺损伤具有独特的免疫调节作用。
Post influenza pneumonia is a leading cause of mortality and morbidity, with mortality rates approaching 60% when bacterial infections are secondary to multi-drug resistant (MDR) pathogens. Staphylococcus aureus, in particular community acquired MRSA (cMRSA), has emerged as a leading cause of post influenza pneumonia. Linezolid (LZD) prevents acute lung injury in murine model of post influenza bacterial pneumonia Mice were infected with HINI strain of influenza and then challenged with cMRSA at day 7, treated with antibiotics (LZD or Vanco) or vehicle 6 hours post bacterial challenge and lungs and bronchoalveolar lavage fluid (BAL) harvested at 24 hours for bacterial clearance, inflammatory cell influx, cytokine/chemokine analysis and assessment of lung injury. Mice treated with LZD or Vanco had lower bacterial burden in the lung and no systemic dissemination, as compared to the control (no antibiotic) group at 24 hours post bacterial challenge. As compared to animals receiving Vanco, LZD group had significantly lower numbers of neutrophils in the BAL (9×103 vs. 2.3×104, p < 0.01), which was associated with reduced levels of chemotactic chemokines and inflammatory cytokines KC, MIP-2, IFN-γ, TNF-α and IL-1β in the BAL. Interestingly, LZD treatment also protected mice from lung injury, as assessed by albumin concentration in the BAL post treatment with H1N1 and cMRSA when compared to vanco treatment. Moreover, treatment with LZD was associated with significantly lower levels of PVL toxin in lungs. Linezolid has unique immunomodulatory effects on host inflammatory response and lung injury in a murine model of post-viral cMRSA pneumonia.
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