title: Oral administration of dextran sodium sulphate induces a caecum-localized colitis in rabbits.
abstract: Trichuris suis ova (TSO) have shown promising results in the treatment of inflammatory bowel disease (IBD) but the mechanisms which underlies this therapeutic effect cannot be studied in mice and rats as T. suis fails to colonize the rodent intestine, whilst hatching in humans and rabbits. As a suitable rabbit IBD model is currently not available, we developed a rabbit colitis model by administration of dextran sodium sulphate (DSS). White Himalayan rabbits (n = 12) received 0.1% DSS in the daily water supply for five days. Clinical symptoms were monitored daily, and rabbits were sacrificed at different time points. A genomewide expression analysis was performed with RNA isolated from caecal lamina propria mononuclear cells (LPMC) and intestinal epithelial cells (IEC). The disease activity index of DSS rabbits increased up to 2.1 ± 0.4 (n = 6) at day 10 (controls <0.5). DSS induced a caecum-localized pathology with crypt architectural distortion, stunted villous surface and inflammatory infiltrate in the lamina propria. The histopathology score reached a peak of 14.2 ± 4.9 (n = 4) at day 10 (controls 7.7 ± 0.9, n = 5). Expression profiling revealed an enrichment of IBD-related genes in both LPMC and IEC. Innate inflammatory response, Th17 signalling and chemotaxis were among the pathways affected significantly. We describe a reproducible and reliable rabbit model of DSS colitis. Localization of the inflammation in the caecum and its similarities to IBD make this model particularly suitable to study TSO therapy in vivo.
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Irina
authors.initials: I
authors.lastname: Leonardi
authors.affiliation: Central Biological Laboratory, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Flora
authors.initials: F
authors.lastname: Nicholls
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Kirstin
authors.initials: K
authors.lastname: Atrott
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Cee
authors.affiliation: Research and Development, Dr. Falk Pharma GmbH, Freiburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Tewes
authors.affiliation: Research and Development, Dr. Falk Pharma GmbH, Freiburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Greinwald
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Isabelle
authors.identifier: http://orcid.org/0000-0002-0125-3072
authors.initials: I
authors.lastname: Frey-Wagner
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001691:Biological Therapy / Q000379:methods; D002432:Cecum / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003092:Colitis / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D020556:Neutrophil Infiltration; D011817:Rabbits; D012720:Severity of Illness Index; D013997:Time Factors; D014258:Trichuris / Q000502:physiology
chemical_list: D018836:Inflammation Mediators; D016264:Dextran Sulfate
keywords: Crohn's disease; DSS colitis; RNA sequencing; Trichuris suis; rabbit model of inflammatory bowel disease; ulcerative colitis