title: The intestinal anti-inflammatory effect of dersalazine sodium is related to a down-regulation in IL-17 production in experimental models of rodent colitis.
abstract: OBJECTIVE
  Dersalazine sodium (DS) is a new chemical entity formed by combining, through an azo bond, a potent platelet activating factor (PAF) antagonist (UR-12715) with 5-aminosalicylic acid (5-ASA). DS has been demonstrated to have anti-inflammatory effects on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats and recently in UC patients in phase II PoC. There is Increasing evidence that Th17 cells have an important role in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to further characterize the anti-inflammatory effects of DS.
  
  
  METHODS
  Effect of DS (10 or 30 mg·kg(-1) b.i.d.) on TNBS-induced colitis in rats was studied after 2 and 7 days with special focus on inflammatory mediators. Additionally, its anti-inflammatory properties were analysed in two different models of dextran sodium sulphate (DSS)-induced colitis, BALB/c and C57BL/6 mice, the latter being dependent on IL-17.
  
  
  RESULTS
  DS, when administered for 7 days, showed intestinal anti-inflammatory effects in TNBS-induced colitis; these effects were observed both macroscopically and through the profile of inflammatory mediators (TNF, IL-1β, IL-6 and IL-17). Although the 2 day treatment with DS did not induce intestinal anti-inflammatory effects, it was sufficient to reduce the enhanced IL-17 expression. DS showed beneficial effects on DSS-induced colitis in C57BL/6 mice and reduced colonic pro-inflammatory cytokines IL-1β, IL-6 and IL-17. In contrast, it did not exert intestinal anti-inflammatory effects on DSS-induced colitis in BALB/c mice.
  
  
  CONCLUSIONS
  DS exerts intestinal anti-inflammatory activity in different rodent models of colitis through down-regulation of IL-17 expression.
authors.affiliation: Centro de Investigaciones Biomédicas en Red - Enfermedades Hepáticas y Digestivas (CIBER-EHD), Department of Pharmacology, Center for Biomedical Research, University of Granada, Granada, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Camuesco
authors.forename: M E
authors.initials: ME
authors.lastname: Rodríguez-Cabezas
authors.forename: N
authors.initials: N
authors.lastname: Garrido-Mesa
authors.forename: M
authors.initials: M
authors.lastname: Cueto-Sola
authors.forename: E
authors.initials: E
authors.lastname: Bailón
authors.forename: M
authors.initials: M
authors.lastname: Comalada
authors.forename: B
authors.initials: B
authors.lastname: Arribas
authors.forename: M
authors.initials: M
authors.lastname: Merlos
authors.forename: D
authors.initials: D
authors.lastname: Balsa
authors.forename: A
authors.initials: A
authors.lastname: Zarzuelo
authors.forename: G
authors.initials: G
authors.lastname: Janer
authors.forename: J
authors.initials: J
authors.lastname: Xaus
authors.forename: J
authors.initials: J
authors.lastname: Román
authors.forename: J
authors.initials: J
authors.lastname: Gálvez
mesh_terms: D000636:Aminosalicylic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001372:Aza Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001391:Azo Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000636:Aminosalicylic Acids; D000893:Anti-Inflammatory Agents; D001372:Aza Compounds; D001391:Azo Compounds; D016207:Cytokines; D010972:Platelet Activating Factor; C571878:dersalazine; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; C419382:UR 12746