Bacterial DNA in patients with cirrhosis and noninfected ascites mimics the soluble immune response established in patients with spontaneous bacterial peritonitis
Bacterial DNA in patients with cirrhosis and noninfected ascites mimics the soluble immune response established in patients with spontaneous bacterial peritonitis
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DOI：
10.1002/hep.22083
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发表时间：
2008-03-01
期刊：
影响因子：
13.5
通讯作者：
Such, Jose
中科院分区：
文献类型：
--
作者：
Frances, Ruben;Zapater, Pedro;Such, Jose
细菌感染和相关炎症反应的严重程度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）易位的天然免疫应答与由活菌易位引起的天然免疫应答，以及细胞因子应答与血清bactDNA水平之间的关系。对226例肝硬化非感染性腹水患者、22例自发性细菌性腹膜炎患者和10例持续使用诺氟沙星的腹水患者进行了bactDNA易位研究。通过酶联免疫吸附试验测定血清和腹水肿瘤坏死因子a、干扰素-γ、白细胞介素-12和一氧化氮代谢产物。通过16 S核糖体RNA基因的扩增和测序以及DNA芯片实验室的数字量化进行细菌基因组鉴定。在77例未感染患者（34%）和所有自发性细菌性腹膜炎病例中，甚至在腹水培养阴性的患者中，都存在bactDNA。诺氟沙星组无一例发生bactDNA易位。所有细胞因子的水平在bactDNA易位或自发性细菌性腹膜炎患者中相似，并且显著高于无bactDNA或接受诺氟沙星治疗的患者。血清bactDNA浓度超过了一系列bactDNA易位或自发性细菌性腹膜炎患者72小时内所有细胞因子和一氧化氮的水平。在一系列自发性细菌性腹膜炎患者中，抗生素治疗并不能在短期内消除bactDNA易位。结论：bactDNA易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难以区分，并且依赖于bactDNA浓度。诺氟沙星消除bactDNA易位和细胞因子反应。
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 a, 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. Conclusion: 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.