Francés Rubén, Zapater Pedro, González-Navajas José M, Muñoz Carlos, Caño Rocío, Moreu Rocío, Pascual Sonia, Bellot Pablo, Pérez-Mateo Miguel, Such José
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
Hepatology. 2008 Mar;47(3):978-85. doi: 10.1002/hep.22083.
Bacterial infections and severity of associated inflammatory reaction influence prognosis in patients with advanced cirrhosis. We compared the innate immune response to bacterial DNA (bactDNA) translocation with that caused by viable bacteria translocation in patients with spontaneous bacterial peritonitis and the relationship between the cytokine response and serum levels of bactDNA. The bactDNA translocation was investigated in 226 patients with cirrhosis and noninfected ascites, 22 patients with spontaneous bacterial peritonitis, and 10 patients with ascites receiving continuous norfloxacin. Serum and ascitic fluid tumor necrosis factor alpha, interferon-gamma, interleukin-12, and nitric oxide metabolites were measured via enzyme-linked immunosorbent assay. Bacterial genomic identifications were made via amplification and sequencing of the 16S ribosomal RNA gene and digital quantization with DNA Lab-on-chips. The bactDNA was present in 77 noninfected patients (34%) and in all cases of spontaneous bacterial peritonitis, even in those with culture-negative ascitic fluid. No patient receiving norfloxacin showed bactDNA translocation. Levels of all cytokines were similar in patients with bactDNA translocation or spontaneous bacterial peritonitis and significantly higher than in patients without bactDNA or in those receiving norfloxacin. Serum bactDNA concentration paralleled levels of all cytokines and nitric oxide in a series of patients with bactDNA translocation or spontaneous bacterial peritonitis followed during 72 hours. Antibiotic treatment in the series of patients with spontaneous bacterial peritonitis did not abrogate bactDNA translocation in the short term.
bactDNA translocation-associated cytokine response is indistinguishable from that in patients with spontaneous bacterial peritonitis and is dependent on bactDNA concentration. Norfloxacin abrogates bactDNA translocation and cytokine response.
细菌感染及相关炎症反应的严重程度会影响晚期肝硬化患者的预后。我们比较了自发性细菌性腹膜炎患者对细菌DNA（bactDNA）移位与活菌移位所产生的先天性免疫反应，以及细胞因子反应与bactDNA血清水平之间的关系。对226例肝硬化合并非感染性腹水患者、22例自发性细菌性腹膜炎患者和10例接受诺氟沙星持续治疗的腹水患者进行了bactDNA移位研究。通过酶联免疫吸附测定法测量血清和腹水肿瘤坏死因子α、干扰素γ、白细胞介素-12和一氧化氮代谢产物。通过16S核糖体RNA基因的扩增和测序以及DNA芯片上的数字量化进行细菌基因组鉴定。bactDNA存在于77例非感染患者（34%）以及所有自发性细菌性腹膜炎病例中，即使是那些腹水培养阴性的病例。接受诺氟沙星治疗的患者均未出现bactDNA移位。bactDNA移位或自发性细菌性腹膜炎患者中所有细胞因子水平相似，且显著高于无bactDNA患者或接受诺氟沙星治疗的患者。在一系列bactDNA移位或自发性细菌性腹膜炎患者中，随访72小时期间，血清bactDNA浓度与所有细胞因子和一氧化氮水平平行。自发性细菌性腹膜炎患者系列中的抗生素治疗在短期内并未消除bactDNA移位。
bactDNA移位相关的细胞因子反应与自发性细菌性腹膜炎患者的反应无法区分，且取决于bactDNA浓度。诺氟沙星可消除bactDNA移位和细胞因子反应。
