title: Bacterial DNA in patients with cirrhosis and noninfected ascites mimics the soluble immune response established in patients with spontaneous bacterial peritonitis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Francés
authors.forename: Pedro
authors.initials: P
authors.lastname: Zapater
authors.forename: José M
authors.initials: JM
authors.lastname: González-Navajas
authors.forename: Carlos
authors.initials: C
authors.lastname: Muñoz
authors.forename: Rocío
authors.initials: R
authors.lastname: Caño
authors.forename: Rocío
authors.initials: R
authors.lastname: Moreu
authors.forename: Sonia
authors.initials: S
authors.lastname: Pascual
authors.forename: Pablo
authors.initials: P
authors.lastname: Bellot
authors.forename: Miguel
authors.initials: M
authors.lastname: Pérez-Mateo
authors.forename: José
authors.initials: J
authors.lastname: Such
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001201:Ascites / Q000150:complications* / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology*; D004269:DNA, Bacterial / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000032:analysis / Q000097:blood; D018664:Interleukin-12 / Q000032:analysis / Q000097:blood; D008103:Liver Cirrhosis / Q000150:complications* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009643:Norfloxacin / Q000494:pharmacology / Q000627:therapeutic use; D010538:Peritonitis / Q000276:immunology* / Q000382:microbiology* / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000097:blood
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D009643:Norfloxacin