title: Inhibition of intestinal bacterial translocation with rifaximin modulates lamina propria monocytic cells reactivity and protects against inflammation in a rodent model of colitis.
abstract: BACKGROUND
  A modification of the intestinal flora and an increased bacterial translocation is a common finding in patients with inflammatory bowel disease as well as in animal model of colitis. Rifaximin, a non-absorbable derivative of rifamycin, is an effective antibiotic that acts by inhibiting bacterial ribonucleic acid synthesis.
  
  
  OBJECTIVE
  In the present study, we investigated the effect of the administration of rifaximin (10, 30 and 50 mg/kg/day) or prednisolone (10 mg/kg/day) in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice.
  
  
  METHODS
  Colitis was induced in mice by intrarectal administration of TNBS (1.5 mg/mouse in 50% ethanol) and disease severity assessed clinically and by histologic scoring of colon damage, determination of interleukin (IL)-2, IL-12, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha (protein and mRNA and myeloperoxidase (MPO) activity in the colon. Cytokines production by the lamina propria mononuclear cells (LPMC) and luminal bacteria were also measured.
  
  
  RESULTS
  Rifaximin administration (30 or 50 mg/kg/day) increased survival rates of colitic mice and reduced colitis severity as demonstrated by improvement of wasting syndrome, histologic scores, decrease in colon IL-2, IL-12, IFN-gamma and TNF-alpha (protein and mRNA) levels, and diminished colon MPO activity. Rifaximin administration caused a significant reduction of colon bacterial translocation towards mesenteric lymph nodes. LPMC obtained from rifaximin-treated mice released significantly lower amount of IFN-gamma in response to ex vivo stimulation with agonistic anti-CD3 and anti-CD28 antibodies. Rifaximin (50 mg/kg/day) significantly accelerates recovery in mice with established colitis.
  
  
  CONCLUSIONS
  Luminal bacterial microflora plays a role in the pathogenesis of TNBS-induced colitis in mice. Rifaximin administration reduces the development of colitis and accelerates healing of established disease by preventing bacterial translocation.
authors.affiliation: Clinica di Gastroenterologia ed Epatologia, Dipartimento di Medicina Clinica, Sperimentale e Farmacologia, Università di Perugia, Perugia, Italy. fiorucci@unipg.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiorucci
authors.forename: Eleonora
authors.initials: E
authors.lastname: Distrutti
authors.forename: Andrea
authors.initials: A
authors.lastname: Mencarelli
authors.forename: Miriam
authors.initials: M
authors.lastname: Barbanti
authors.forename: Ernesto
authors.initials: E
authors.lastname: Palazzini
authors.forename: Antonio
authors.initials: A
authors.lastname: Morelli
mesh_terms: D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018988:Bacterial Translocation / Q000187:drug effects*; D003092:Colitis / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D007371:Interferon-gamma / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008198:Lymph Nodes / Q000382:microbiology; D008643:Mesentery; D051379:Mice; D008807:Mice, Inbred BALB C; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D011239:Prednisolone / Q000627:therapeutic use; D012294:Rifamycins / Q000627:therapeutic use*; D000078262:Rifaximin; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D012294:Rifamycins; D007371:Interferon-gamma; D014302:Trinitrobenzenesulfonic Acid; D011239:Prednisolone; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000078262:Rifaximin