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首页> 外文期刊>Cytokine >Impact of microbial tolerance in persistent secondary Klebsiella pneumoniae peritonitis.
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Impact of microbial tolerance in persistent secondary Klebsiella pneumoniae peritonitis.

机译:持续性继发性肺炎克雷伯菌腹膜炎中微生物耐受性的影响。

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PURPOSE AND METHODS: Microbial tolerance represents a diminished pro-inflammatory response following repeated stimulation by a host of pathogen-associated molecular patterns (PAMPs) of varying origins. Toll-like receptors (TLRs) have been centrally implicated in the development of tolerance. The purpose of this study was to investigate the impact of tolerance in a previously described murine model. C57BL/6 mice were pretreated intraperitoneally with phosphate buffered saline (PBS), heat-killed Klebsiella 2x10(8) CFU (hkKlebsiella), LPS 10mg/kg (LPS 10), or BLP 10mg/kg (BLP 10). Following pretreatment, peritonitis was induced 24h later using 10(3) intraperitoneal Klebsiella CFU. Peritoneal concentrations of TNF-alpha, IL-10 and nitric oxide (NO), as well as characteristic cell patterns, were determined. Long-term consequences of microbial tolerance were assessed by measuring survival and weight-loss. RESULTS: Following in vitro stimulation with Klebsiella 10(5) and 10(3) CFU, TNF-alpha and IL-10 secretion were diminished in macrophages harvested from mice pretreated with hkKlebsiella, LPS 10 and BLP 10. Pretreated animals had significantly lower bacterial counts. Conversely, local NO levels were elevated. Survival was not different between the groups. CONCLUSION: Pretreatment with TLR ligands induced microbial tolerance, with reduced peritoneal cytokine concentrations and enhanced early bacterial clearance. However, this did not translate into improved survival.
机译:用途和方法:微生物耐受性代表由多种不同来源的病原体相关分子模式(PAMP)反复刺激后减弱的促炎反应。 Toll样受体(TLRs)在耐受性的发展中已被集中牵连。这项研究的目的是调查在先前描述的小鼠模型中耐受性的影响。 C57BL / 6小鼠腹腔内用磷酸盐缓冲液(PBS),热灭活的克雷伯菌2x10(8)CFU(hkKlebsiella),LPS 10mg / kg(LPS 10)或BLP 10mg / kg(BLP 10)进行腹膜内预处理。预处理后,使用10(3)腹膜内克雷伯菌CFU诱导腹膜炎24小时。确定了腹膜中TNF-α,IL-10和一氧化氮(NO)的浓度,以及特征性的细胞模式。通过测量存活率和体重减轻来评估微生物耐受的长期后果。结果:在体外用克雷伯菌10(5)和10(3)CFU刺激后,从用hkKlebsiella,LPS 10和BLP 10预处理的小鼠收获的巨噬细胞中,TNF-α和IL-10的分泌减少。计数。相反,局部NO水平升高。两组之间的生存率没有差异。结论:TLR配体预处理可诱导微生物耐受,降低腹膜细胞因子浓度并增强早期细菌清除率。但是,这并未转化为存活率的提高。

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