title: Effects of retinoids in mouse models of colitis: benefit or danger to the gastrointestinal tract?
abstract: BACKGROUND
  In vitro and in vivo data have shown that retinoid treatment promotes an anti-inflammatory milieu with few adverse effects toward the gastrointestinal tract. The in vivo studies reported here further evaluate retinoid effects in 2 mouse models of inflammatory bowel disease.
  
  
  METHODS
  Chronic dextran sulfate sodium colitis was induced in age- and weight-matched C57Bl/6 mice by 4 cycles of dextran sulfate sodium administration (6-8 animals/group). At cycle 4, animals were administered 13-cis-retinoic acid (isotretinoin, 30 mg/kg) or vehicle (oral gavage) or 4-oxo-13-cis-retinoic acid (15 mg/kg, intraperitoneal) daily. T-cell transfer colitis was induced in CB17 SCID mice by transfer of naive CD4CD62L T cells and treated by transfer of regulatory CD4CD25 T cells (4-6 animals/group); isolated from BALB/c mice after treatment with isotretinoin or vehicle, as above, for 2 weeks. Assessments included endoscopic and histological scores, myeloperoxidase activity, serum cytokines, and plasma isotretinoin levels.
  
  
  RESULTS
  Retinoid-treated animals with colitis showed comparable changes in myeloperoxidase activity, and endoscopic and histological scores, versus untreated animals with colitis. Modest and comparable changes were seen in body weight and colon length in animals injected with naive T cells from isotretinoin-treated donors versus those injected with T cells from vehicle-treated donors. Retinoid treatment was consistently associated with lower interleukin-12 levels, which, after the transfer of naive T cells from isotretinoin-treated donors, supported isotretinoin-mediated predisposition of naive T cells toward reduced proinflammatory cytokine expression. Colitis had no effect on isotretinoin exposure.
  
  
  CONCLUSIONS
  Retinoids attenuate the proinflammatory cytokine response in vivo, with only modest effects on body weight and parameters of gastrointestinal morphology.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Frey-Wagner
authors.forename: Anne
authors.initials: A
authors.lastname: Fischbeck
authors.forename: Alexandra
authors.initials: A
authors.lastname: Cee
authors.forename: Irina
authors.initials: I
authors.lastname: Leonardi
authors.forename: Sven
authors.initials: S
authors.lastname: Gruber
authors.forename: Eugenia
authors.initials: E
authors.lastname: Becker
authors.forename: Kirstin
authors.initials: K
authors.lastname: Atrott
authors.forename: Silvia
authors.initials: S
authors.lastname: Lang
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003879:Dermatologic Agents / Q000494:pharmacology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D015474:Isotretinoin / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009195:Peroxidase / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines; D003879:Dermatologic Agents; D016264:Dextran Sulfate; D009195:Peroxidase; D015474:Isotretinoin