Servicio de Microbiología and CIBER en Epidemiología y Salud Pública (CIBERESP), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain.
PLoS One. 2011;6(12):e29577. doi: 10.1371/journal.pone.0029577. Epub 2011 Dec 28.
Cystic Fibrosis (CF) is an inherited pleiotropic disease that results from abnormalities in the gene codes of a chloride channel. The lungs of CF patients are chronically infected by several pathogens but bacteraemia have rarely been reported in this pathology. Besides that, circulating monocytes in CF patients exhibit a patent Endotoxin Tolerance (ET) state since they show a significant reduction of the inflammatory response to bacterial stimulus. Despite a previous description of this phenomenon, the direct cause of ET in CF patients remains unknown. In this study we have researched the possible role of microbial/endotoxin translocation from a localized infection to the bloodstream as a potential cause of ET induction in CF patients. Plasma analysis of fourteen CF patients revealed high levels of LPS compared to healthy volunteers and patients who suffer from Chronic Obstructive Pulmonary Disease. Experiments in vitro showed that endotoxin concentrations found in plasma of CF patients were enough to induce an ET phenotype in monocytes from healthy controls. In agreement with clinical data, we failed to detect bacterial DNA in CF plasma. Our results suggest that soluble endotoxin present in bloodstream of CF patients causes endotoxin tolerance in their circulating monocytes.
囊性纤维化（CF）是一种遗传性多效性疾病，由氯离子通道基因编码异常引起。CF 患者的肺部会受到多种病原体的慢性感染，但这种病理情况下很少报告菌血症。此外，CF 患者的循环单核细胞表现出明显的内毒素耐受（ET）状态，因为它们对细菌刺激的炎症反应显著减少。尽管之前已经描述了这种现象，但 CF 患者 ET 的直接原因仍不清楚。在这项研究中，我们研究了微生物/内毒素从局部感染向血液转移作为 CF 患者 ET 诱导的潜在原因的可能性。对 14 名 CF 患者的血浆分析显示，与健康志愿者和慢性阻塞性肺疾病患者相比，LPS 水平较高。体外实验表明，CF 患者血浆中的内毒素浓度足以诱导健康对照者单核细胞的 ET 表型。与临床数据一致，我们未能检测到 CF 血浆中的细菌 DNA。我们的结果表明，CF 患者血液中存在的可溶性内毒素导致其循环单核细胞对内毒素耐受。
