Effective treatment of mouse experimental colitis by alpha 2 integrin antibody : comparison with alpha 4 antibody and conventional therapy

• Aim To compare the therapeutic effect of a2 and a4 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 2.53.0% 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-a2 antibodies and methotrexate reduced the body weight loss. At the end of treatment, anti-a2 antibodies reduced rectal bleeding, while methotrexate reduced the disease activity index score. Histological evaluation showed that anti-a2 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-1 beta at the mRNA level, while the anti-a2 antibody group displayed decreased protein expression of iNOS and IL-1 beta. Conclusions Specific blocking of extravascular trafficking of leucocytes with a2-antibodies could be a new beneficial drug target in inflammatory bowel disease.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Gastroenterologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

Nyckelord

CD49b antigen

CD49d antigen

dextran sulphate

inflammatory bowel disease

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