Published online Nov 7, 2015. doi: 10.3748/wjg.v21.i41.11493
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.
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.