RESOLUTION OF MUCOSAL INFLAMMATION AND FALL IN IL-1 BETA mRNA IN ACTIVE CROHN'S DISEASE IN RESPONSE TO POLYMERIC DIET CT3211.

Abstract

Enteral nutrition (EN) is an established therapy in the treatment of active Crohn's disease (CD), although the mechanism of its action is uncertain. 15 children (10.4-16.3 years) with active CD (8 newly diagnosed, 7 in relapse) were treated exclusively with a new oral polymeric diet (containing whole casein as the protein source), for 8 weeks. Before and after treatment, subjects were assessed clinically (modified Lloyd Still index), biochemically (CRP), endoscopically, histologically and for IL-1 beta mRNA (8/15 cases) in ileal, caecal and colonic biopsies by quantitative RT-PCR. All newly diagnosed, and 5/7 relapsed cases responded to EN (complete remission in 9/15). The 2 treatment failures had severe colonic disease and an appendiceal abscess. CRP declined with treatment (from median 20 to 1.0 mg/l, p<0.0001). Endoscopic appearance scored from 0 (normal) to 3 (severe disease) improved in the terminal ileum (TI) (from median 2.0 to 0.5, p<0.05), but not significantly in colon (unchanged at median score 1.0). Histology scored from 0 (normal) to 3 (severe inflammation with ulceration) improved significantly in TI (from median 1.5 to 0.5, p<0.05) but not in the colon (2.0 to 1.0, p=0.07). There was a decrease in IL-1 beta mRNA at all sites biopsied (caecum and colon: median 1.36 ×105 to 2.55 ×104, and 8.65 ×104 to 9.5 ×103 transcripts mRNA/ug RNA), which in the TI achieved significance (decline from median 5.53 ×106 to 5 ×103 transcripts mRNA/ug RNA; p<0.01). In active CD the clinical response to polymeric diet CT3211 is associated with mucosal healing, and a fall in mucosal mRNA of the pro-inflammatory cytokine IL-1 beta.