Treatment with non-selective beta-blockers affects the systemic inflammatory response to bacterial DNA in patients with cirrhosis

Liver Int. 2018 Dec;38(12):2219-2227. doi: 10.1111/liv.13890. Epub 2018 Jun 19.

Abstract

Background & aims: The use of non-selective beta-blockers has been associated with lower rates of infection and reduced infection-associated morbidity in patients with cirrhosis. However, it is unknown if these drugs modify the systemic inflammatory response to circulating bacterial DNA.

Methods: Sixty-three patients with cirrhosis were included during an episode of decompensation by ascites. Thirty of those patients were on beta-blockers. Blood samples were obtained after each patient had been in the supine position for at least 30 minutes in a quiet atmosphere. Bacterial DNA, serum cytokines, nitric oxide, and LPS were determined. Phagocytic and oxidative burst activities were determined in polymorphonuclear cells from the patients.

Results: The detection rate of bacterial DNA in the blood was the same (33%) for patients not treated and treated with non-selective beta-blockers. Patients naive to non-selective beta-blockers showed significantly higher serum levels of IL6, IFN-gamma and IL10 in response to the presence of bacterial DNA. Patients treated with non-selective beta-blockers showed higher basal inflammatory activity that did not change with the presence of bacterial DNA. Monocytes and granulocytes from patients treated with non-selective beta-blockers showed a significantly increased phagocytic capacity in the presence of bacterial DNA.

Conclusions: In patients with cirrhosis, chronic treatment with beta-blockers is associated with a higher unstimulated production of serum cytokines and an increased phagocytic activity in the presence of bacterial DNA.

Keywords: bacterial DNA; cirrhosis; inflammation; non-selective beta-blockers; sympathetic nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / adverse effects
  • Adrenergic beta-Antagonists / therapeutic use*
  • Aged
  • Ascites / microbiology
  • Ascitic Fluid / microbiology
  • Bacterial Translocation / drug effects
  • Cytokines / blood
  • DNA, Bacterial / blood*
  • Female
  • Humans
  • Hypertension, Portal / complications
  • Hypertension, Portal / drug therapy*
  • Inflammation / drug therapy*
  • Linear Models
  • Liver Cirrhosis / physiopathology*
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Multivariate Analysis
  • Neutrophils / drug effects
  • Nitric Oxide / blood
  • Prospective Studies
  • Respiratory Burst / drug effects*

Substances

  • Adrenergic beta-Antagonists
  • Cytokines
  • DNA, Bacterial
  • Nitric Oxide