Modulation of adhesion molecule expression that govern trafficking of leukocytes into the inflamed intestine is envisioned as a new strategy for treatment of
inflammatory bowel disease (IBD). This study was designed to determine the impact of reducing oxidative stress on adhesion molecules expression and leukocyte recruitment in experimental chronic
colitis. For that purpose, colitic
interleukin-10 knockout and wild-type mice were studied. Groups of animals were treated with
Cu/Zn superoxide dismutase (SOD1) 13 mg/kg/d or vehicle for either 7 or 14 days. Expression of
vascular cell adhesion molecule-1 and mucosal addressin
cell adhesion molecule-1 were determined; leukocyte-endothelial cell interactions in colonic venules were studied with intravital microscopy; and changes in colon pathology and
biomarkers of
colitis severity were determined. Development of
colitis was associated with a marked increase in endothelial
vascular cell adhesion molecule-1 and mucosal addressin
cell adhesion molecule-1 expression, which were significantly reduced by treatment with SOD1. The increase in leukocyte rolling and adhesion in colonic venules of colitic mice were significantly reduced by administration of SOD1. This treatment markedly reduced colonic
lipid hydroperoxidation, myeoloperoxidase activity, and plasma levels of
serum amyloid A protein and resulted in significant, although modest, reductions in histologic damage score. The therapeutic value of SOD1 when administered prophylactically was assessed in the
dextran sulfate sodium model of
colitis with similar positive results. These results indicate that SOD1 affords significant amelioration of colonic inflammatory changes in experimental
colitis. Down-regulation of adhesion molecule expression, reduction of
lipid hydroperoxidation, and recruitment of leukocytes into the inflamed intestine contribute to this beneficial effect.