title: Immunomodulating effects of antibiotics used in the prophylaxis of bacterial infections in advanced cirrhosis.
abstract: 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.
authors.affiliation: Pedro Zapater, José Manuel González-Navajas, Rubén Francés, CIBERehd, Hospital General Universitario de Alicante, 03010 Alicante, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Zapater
authors.affiliation: Pedro Zapater, José Manuel González-Navajas, Rubén Francés, CIBERehd, Hospital General Universitario de Alicante, 03010 Alicante, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: González-Navajas
authors.affiliation: Pedro Zapater, José Manuel González-Navajas, Rubén Francés, CIBERehd, Hospital General Universitario de Alicante, 03010 Alicante, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Such
authors.affiliation: Pedro Zapater, José Manuel González-Navajas, Rubén Francés, CIBERehd, Hospital General Universitario de Alicante, 03010 Alicante, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Francés
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D019072:Antibiotic Prophylaxis; D001419:Bacteria / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D001424:Bacterial Infections / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D018988:Bacterial Translocation / Q000187:drug effects; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000276:immunology; D007422:Intestines / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D008103:Liver Cirrhosis / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D009643:Norfloxacin / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D007155:Immunologic Factors; D018836:Inflammation Mediators; D009643:Norfloxacin
keywords: Bacterial DNA; Cirrhosis; Cytokines; Norfloxacin; Prophylaxis