Grade of soluble inflammatory response is mainly affected by circulating bacterial DNA concentrations in cirrhosis

Liver Int. 2016 Oct;36(10):1473-80. doi: 10.1111/liv.13118. Epub 2016 Apr 28.

Abstract

Background & aims: Patients with decompensated cirrhosis show a marked innate immune response that shows a wide variability. The reasons for this fact have not been previously evaluated. This investigation was undertaken to study factors influencing the immune response intensity in both serum and ascitic fluid in patients with cirrhosis and ascites with presence of bactDNA.

Methods: 77 patients with cirrhosis and presence of bactDNA fragments in blood and ascitic fluid were included. Identification of bactDNA was evaluated by 16SrRNA gene PCR followed by nucleotide sequencing and by species-specific PCR. Concentration of amplified bacterial-DNA, bacteria identification, LPS, TNF-alpha, IFN-gamma, Interleukin 12 and nitric oxide in serum and ascitic fluid were evaluated as factors related to intensity of the immune response.

Results: Serum and AF levels of bactDNA, TNF-α, IFN-γ and nitric oxide concentration were higher in patients with presence of bactDNA from gram negative bacteria. Serum TNF-α levels showed a significant correlation with concentrations of bactDNA (r = 0.88; P = 0.001) and LPS (r = 0.28; P = 0.016). Serum nitric oxide levels were also significantly correlated with concentrations of bactDNA (r = 0.761; P = 0.001) but not with LPS levels. Levels of INF-γ and IL-12 were not significantly correlated with either bactDNA nor LPS levels. Plasmatic concentration of bactDNA was the most accurately correlated factor with the inflammatory response (ancova model included only levels of bactDNA (r(2) = 0.87, P = 0.047 for TNF-α; r(2) = 0.45, P = 0.03 for NOx).

Conclusions: Bacterial-DNA concentration is the most influencing variable associated with serum TNF-α and nitric oxide response.

Keywords: ascitic fluid; bacterial translocation; cirrhosis; cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Ascites / immunology
  • Ascites / microbiology
  • Ascitic Fluid / microbiology
  • Bacterial Translocation*
  • DNA, Bacterial / blood*
  • Female
  • Humans
  • Immunity, Innate
  • Interferon-gamma / blood
  • Interleukin-12 / blood
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / immunology*
  • Male
  • Middle Aged
  • Nitric Oxide / blood*
  • Polymerase Chain Reaction
  • Prospective Studies
  • Spain
  • Tumor Necrosis Factor-alpha / blood*

Substances

  • DNA, Bacterial
  • IFNG protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Nitric Oxide
  • Interferon-gamma