We developed a
colitis model in Syrian hamsters (Mesocricetus auratus) to investigate the relationship between
colitis and
neutrophil elastase (NE).
Colitis was induced by a single intracolonic dose of trinitrobenzene
sulfonic acid (TNBS; 90 mg/ml) dissolved in 15% (vol/vol)
ethanol. The
ulcer area, tissue
myeloperoxidase (MPO) activity, and
luminal NE activity all were increased on Days 1 and 5, corresponding with the acute inflammatory histopathological changes. These acute inflammatory parameters subsequently decreased by Day 14, and chronic inflammatory histopathological changes became evident. Recurrence of
inflammation was not observed during the period up to Day 28. To evaluate our
colitis model, the effects of
prednisolone were examined.
Prednisolone was administered orally once on the day before induction of
colitis, and animals were treated twice daily thereafter. Although
prednisolone had little effect on the tissue MPO activity,
prednisolone inhibited the
ulcer area and NE activity. In addition, the effects of an NE-specific inhibitor (ONO-6818) on our TNBS-induced
colitis model were examined. In the subcutaneous treatment study,
ONO-6818 was administered once before the induction of
colitis. Although
ONO-6818 had little effect on the tissue MPO activity, the
ulcer area and NE activity were decreased in the ONO-6818-treated group. The inhibitory effects on the
ulcer area and NE activity were confirmed after oral treatment with
ONO-6818 after induction of
colitis. We conclude that our
colitis model is useful for investigating the relationship between
colitis and NE, and inhibition of NE activity can prevent the progression of ulceration.