The effectiveness of steroids in the prevention of bowel strictures depends on the timing of administration

Abstract

Corticosteroids are commonly employed in the treatment of Crohn's at different stages of the disease. We investigated the pathogenesis of stricture formation in the trinitrobenzenesulfonic acid (TNB) model of chronic colitis and the effects of steroids on this process. Colitis was induced by TNB (60 mg in 20% EtOH) in 3 groups of rats (n = 20-25): tnb received no further treatment, dexa-1 received 0.5 mg/kg dexamethasone during the early stage of colitis (.days 1 to 7 after TNB), and dexa-2 received 0.5 mg/kg dexamethasone during the chronic stage (days 7 to 21); controls received no TNB. Rats (8-10 per group) were killed on days 7 and 21. At these times, blood samples were obtained for analysis of transforming growth factor &l (TGF61, elisa), colonic weight and lesions were determined, and the colon was homogenized for measurement of collagen (hydroxyproline) and conagenase activity. A t day 7, there was no difference between controls and tnb in plasma TGF&,, tissue collagen content and collagenase activity. Dexamethasone had no effect at this stage. However, at day 21 marked and significant differences were observed (see table): TGFf$1 Weight Collagen Collagenase ng/mL g/cm pg/mg U/mg protein controls 2 3 ± 3 0 .09±0 .02 2±1 1 5 ± 2 tnb 1 2 9 ± 4 2 0 .58+0 .05* 2 4 ± 2 * 9 + 3 dexa-1 1 1 0 ± 2 5 0 . 5 2 ± 0 . 0 7 * 2 5 ± 7 * 1 5 ± 2 dexa-2 6 5 ± 3 4 0 . 2 4 ± 0 . 0 3 * 5 ± 3 17+3 *P<0.05 vs. controls Moreover, 7 out of 8 tnb rats and 6 out of 8 dexa-1 presented colonic strictures whereas only 1 out of 8 in dexa-2 did (P<0.05). In conclusion, high plasma levels of TGFI~ in the chronic stage of colitis are associated with collagen deposition in the inflamed colon and formation of strictures. Early steroid treatment does not prevent the fibrogenic process. Steroids only protect against stricture formation when administered during the chronic phase. HIGHER TITRES OF ANTINEUTROPHIL CYTOPLASMIC