Validation of murine dextran sulfate sodium-induced colitis using four therapeutic agents for human inflammatory bowel disease.
Dextran sulfate sodium (DSS)-induced colitis is one of the most frequently used rodent models for inflammatory bowel disease (IBD). The aim of this study was to validate the murine DSS-induced colitis model using four therapeutic agents for IBD. C57BL/6 mice were exposed to 3% DSS for 5days followed by 7-9 days of water (acute inflammation) or 20-31 days of water (chronic phase). Clinical symptoms, plasma and colonic inflammatory markers and histology were assessed for the efficacy of cyclosporine A (CsA), methotrexate or anti-IL-12p40 in acute colitis and of anti-IL-12p40 or an agonistic anti-CD3 antibody in chronic colitis. Cyclosporine A and anti-IL-12p40 (in the acute phase) and anti-CD3 (in the chronic phase) treatment attenuated local cytokine levels, improved clinical symptoms (CsA and anti-IL-12p40) and histology (CsA and anti-CD3). Further, anti-IL-12p40 treatment was partly efficacious in the chronic phase, whereas methotrexate showed no efficacy in the acute colitis. Thus, three of the current tested agents showed efficacy in the disease model, arguing that DSS-induced colitis can be used as a relevant model for the translation of mice data to human disease.
Melgar
Silvia
S
Department of Integrative Pharmacology, AstraZeneca R&D Mölndal, Sweden. s.melgar@ucc.ie
Karlsson
Lisa
L
Rehnström
Erika
E
Karlsson
Agneta
A
Utkovic
Helena
H
Jansson
Liselotte
L
Michaëlsson
Erik
E
D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000627:therapeutic use; D017252:CD3 Complex / Q000276:immunology*; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D053762:Interleukin-12 Subunit p40 / Q000276:immunology / Q000378:metabolism*; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL
D000906:Antibodies; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D053762:Interleukin-12 Subunit p40; D016572:Cyclosporine; D016264:Dextran Sulfate; D008727:Methotrexate