title: Role of interleukin 10 in norfloxacin prevention of luminal free endotoxin translocation in mice with cirrhosis.
abstract: OBJECTIVE
  Bacterial endotoxin is present in patients with advanced cirrhosis and can induce an immunogenic response without an overt infection. Norfloxacin is a gram-negative bactericidal drug able to maintain low endotoxin levels and stimulate IL-10 production. We aimed at investigating the role of IL-10 in decreasing endotoxin absorption in cirrhotic mice treated with norfloxacin.
  
  
  METHODS
  Cirrhosis was induced by carbon tetrachloride or bile duct ligation in wild type and IL10-deficient mice with or without norfloxacin prior to an intragastrical administration of E. coli, K. pneumonia or E. faecalis. Spontaneous and induced bacterial translocation, free endotoxin and cytokine levels were evaluated in mesenteric lymph nodes. Intestinal permeability was followed by fluorimetry and barrier integrity markers were measured in disrupted intestinal samples. The inflammatory-modulating mechanism was characterized in purified intestinal mononuclear cells.
  
  
  RESULTS
  Norfloxacin reduced spontaneous and induced MLN positive-cultures in wild type and IL-10-deficient animals. However, reduction of free endotoxin levels was associated with norfloxacin in wild type but not in IL-10-deficient mice. Wild type but not IL-10-deficient mice treated with norfloxacin significantly normalized intestinal permeability and improved gut barrier integrity markers. The toll-like receptor 4-mediated pro-inflammatory milieu was modulated by norfloxacin in a concentration-dependent manner in cultured intestinal mononuclear cells of wild type mice but not of IL-10-deficient mice. The restoration of IL-10 levels in IL-10-deficient animals reactivated the norfloxacin effect on inflammatory-modulation, gut barrier permeability, and luminal endotoxin absorption.
  
  
  CONCLUSIONS
  Norfloxacin not only reduces gram-negative intestinal flora but also participates in an IL-10-driven modulation of gut barrier permeability, thus reducing luminal free endotoxin absorption in experimental cirrhosis.
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Unidad Hepática, Hospital General Universitario de Alicante, Alicante, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gómez-Hurtado
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Unidad Hepática, Hospital General Universitario de Alicante, Alicante, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Moratalla
authors.affiliation: Ecología Microbiana y Nutrición, Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas (IATA-CSIC), Valencia, Spain.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Moya-Pérez
authors.affiliation: Servicio de Anatomía Patológica, Hospital General Universitario de Alicante, Alicante, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Peiró
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Unidad de Farmacología Clínica, Hospital General Universitario de Alicante, Alicante, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Zapater
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Unidad Hepática, Hospital General Universitario de Alicante, Alicante, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: González-Navajas
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Giménez
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Departamento de Medicina Clínica, Facultad de Medicina, Universidad Miguel Hernández, San Juan de Alicante, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Such
authors.affiliation: Ecología Microbiana y Nutrición, Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas (IATA-CSIC), Valencia, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Sanz
authors.affiliation: CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Unidad Hepática, Hospital General Universitario de Alicante, Alicante, Spain; Departamento de Medicina Clínica, Facultad de Medicina, Universidad Miguel Hernández, San Juan de Alicante, Spain. Electronic address: frances_rub@gva.es.
authors.forename: Rubén
authors.initials: R
authors.lastname: Francés
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018988:Bacterial Translocation / Q000187:drug effects / Q000276:immunology; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000502:physiology; D008106:Liver Cirrhosis, Experimental / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009643:Norfloxacin / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D004731:Endotoxins; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D009643:Norfloxacin
keywords: Cirrhosis; Endotoxin; Interleukin 10; Norfloxacin