title: Effective treatment of mouse experimental colitis by alpha 2 integrin antibody: comparison with alpha 4 antibody and conventional therapy.
abstract: OBJECTIVE
  To compare the therapeutic effect of α(2) and α(4) integrin-blocking antibodies to conventional inflammatory bowel disease drugs methotrexate, 5-aminosalicylic acid and azathioprine in the dextran sulphate sodium mouse colitis model.
  
  
  METHODS
  Colitis was induced in balb/c mice with 2.5-3.0% dextran sulphate sodium. Treatment was given daily for 7 days after the onset of colitis, by rectal installation. Clinical signs of disease were assessed daily using a disease activity index. After 19 days, all animals were killed and colon samples collected for histological grading and mRNA/protein analysis. All treatment groups were compared with an untreated control group and a treatment group receiving dextran sulphate sodium alone to monitor the potential degree of clinical remission.
  
  
  RESULTS
  Treatment with anti-α(2) antibodies and methotrexate reduced the body weight loss. At the end of treatment, anti-α(2) antibodies reduced rectal bleeding, while methotrexate reduced the disease activity index score. Histological evaluation showed that anti-α(2) antibodies, methotrexate, 5-aminosalicylic acid and azathioprine treatment reduced the acute inflammation; methotrexate was the only treatment with effect on the crypt score. Compared with the dextran sulphate sodium alone group, the methotrexate group showed down-regulation of IL-1β at the mRNA level, while the anti-α(2) antibody group displayed decreased protein expression of iNOS and IL-1β.
  
  
  CONCLUSIONS
  Specific blocking of extravascular trafficking of leucocytes with α(2)-antibodies could be a new beneficial drug target in inflammatory bowel disease.
authors.affiliation: Department of Medicine, Gastroenterology Unit, Karolinska Institutet, Stockholm, Sweden. linda.gillberg@ki.se
authors.forename: L
authors.initials: L
authors.lastname: Gillberg
authors.forename: S
authors.initials: S
authors.lastname: Berg
authors.forename: P J
authors.initials: PJ
authors.lastname: de Verdier
authors.forename: L
authors.initials: L
authors.lastname: Lindbom
authors.forename: J
authors.initials: J
authors.lastname: Werr
authors.forename: P M
authors.initials: PM
authors.lastname: Hellström
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019138:Antibodies, Blocking / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D039421:Integrin alpha2 / Q000378:metabolism*; D039441:Integrin alpha4 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000893:Anti-Inflammatory Agents; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D039421:Integrin alpha2; D039441:Integrin alpha4