Veterans Affairs Medical Center, Louisville, KY, USA.
Cytokine. 2011 Jan;53(1):84-93. doi: 10.1016/j.cyto.2010.08.012.
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 2×10(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-α, 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.
Following in vitro stimulation with Klebsiella 10(5) and 10(3) CFU, TNF-α 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.
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.
微生物耐受性是指在受到不同来源的病原体相关分子模式（PAMPs）的反复刺激后，促炎反应减弱。Toll 样受体（TLRs）被认为是耐受性发展的核心因素。本研究的目的是在之前描述的小鼠模型中研究耐受性的影响。C57BL/6 小鼠经腹腔内预先用磷酸盐缓冲盐水（PBS）、热灭活肺炎克雷伯氏菌 2×10(8)CFU（hkKlebsiella）、LPS 10mg/kg（LPS 10）或 BLP 10mg/kg（BLP 10）预处理。预处理后 24 小时，用 10(3)腹腔内肺炎克雷伯氏菌 CFU 诱导腹膜炎。测定 TNF-α、IL-10 和一氧化氮（NO）的腹膜浓度以及特征性细胞模式。通过测量存活率和体重减轻来评估微生物耐受性的长期后果。
用肺炎克雷伯氏菌 10(5)和 10(3)CFU 体外刺激后，来自 hkKlebsiella、LPS 10 和 BLP 10 预处理小鼠的巨噬细胞中 TNF-α 和 IL-10 的分泌减少。预处理动物的细菌计数明显较低。相反，局部 NO 水平升高。各组之间的存活率没有差异。
TLR 配体预处理诱导了微生物耐受性，腹膜细胞因子浓度降低，早期细菌清除增强。然而，这并没有转化为更好的存活率。
