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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2015; 21(41): 11493-11501
Published online Nov 7, 2015. doi: 10.3748/wjg.v21.i41.11493
Immunomodulating effects of antibiotics used in the prophylaxis of bacterial infections in advanced cirrhosis
Pedro Zapater, José Manuel González-Navajas, José Such, Rubén Francés
Pedro Zapater, José Manuel González-Navajas, Rubén Francés, CIBERehd, Hospital General Universitario de Alicante, 03010 Alicante, Spain
José Such, Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
Rubén Francés, Departamento Medicina Clínica, Universidad Miguel Hernández, 03550 San Juan, Spain
Author contributions: All authors contributed to this manuscript.
Supported by Grants PI13/1443 and PI14/01090 from Instituto de Salud Carlos III, Madrid, Spain, and FEDER funds, EU.
Conflict-of-interest statement: All authors declare that they have no competing interests with any financial organization regarding the material discussed in the manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Rubén Francés, PhD, CIBERehd, Hospital General Universitario de Alicante, Avda. Pintor Baeza 12, 03010 Alicante, Spain.
Telephone: +34-965-913928 Fax: +34-965-913922
Received: April 10, 2015
Peer-review started: April 11, 2015
First decision: May 18, 2015
Revised: May 29, 2015
Accepted: August 31, 2015
Article in press: August 31, 2015
Published online: November 7, 2015

The use of norfloxacin either as primary or secondary prophylaxis of bacterial infections in advanced cirrhosis has improved patient’s survival. This may be explained not only due to a significant decrease in the number of infections, but also because of a direct immunomodulatory effect. Selective intestinal decontamination with norfloxacin reduces translocation of either viable bacteria or bacteria-driven products from the intestinal lumen. In addition, norfloxacin directly modulates the systemic inflammatory response. The pro-inflammatory cytokine profile secreted by neutrophils from these patients shows a close, significant, and inverse correlation with serum norfloxacin levels. Similar effects have been described with other quinolones in different clinical conditions. Although the underlying mechanisms are not well defined for most of the antibiotics, the pathways triggered for norfloxacin to induce such immunomodulatory effects involve the down-regulation of pro-inflammatory inducible nitric oxide synthase, cyclooxygenase-2, and NF-κB and the up-regulation of heme-oxygenase 1 and IL-10 expression. The knowledge of these immunomodulatory effects, additional to their bactericidal role, improves our comprehension of the interaction between antibiotics and the cellular host response and offer new possibilities for the development of new therapeutic strategies to manage and prevent bacterial infections in cirrhosis.

Keywords: Cirrhosis, Prophylaxis, Cytokines, Bacterial DNA, Norfloxacin

Core tip: The use of antibiotic therapy to either treat or prevent frequent bacteria-derived complications arising in patients with cirrhosis is well established. The knowledge of antibiotic immunomodulatory mechanism, additional to their bactericidal role, improves our comprehension of the interaction between these molecules and the cellular machinery, and provides insight on the development of alternative strategies in the management and prevention of bacterial infections in cirrhosis.