G E Wild1, K A Waschke, A Bitton, A B R Thomson. 1. Department of Medicine, Division of Gastroenterology, McGill University, Montreal, Canada. gary.wild@muhc.mcgill.ca
Abstract
BACKGROUND: The clinical course of Crohn's disease after the induction of remission with medical therapy is characterized by unpredictable relapse. AIM: To evaluate three surrogate markers, intestinal permeability, mucosal TNFalpha and nuclear factor (NF)-kappaB/IkappaBalpha expression, in order to determine the relationship of these parameters to clinical relapse. METHODS: Thirty patients with active Crohn's disease were treated with a 10 week course of prednisone using a tapering dosing regimen. Intestinal permeability (lactulose/mannitol [L/M ratio]) was determined at baseline and at the end of prednisone tapering. TNFalpha production and the levels of expression of NF-kappaB/IkappaBalpha were measured in colonic mucosal biopsies obtained after the induction of remission. RESULTS: Twenty-two patients (73%) achieved remission and 50% of patients experienced a clinical relapse during the ensuing 12 months. Treatment with prednisone resulted in a significant decrease in the L/M ratio. Of the patients that relapsed, 75% had a raised L/M ratio at the time of remission compared with 20% of patients with a normal L/M ratio (P < 0.008; hazard ratio = 6.094; CI 1.55, 17.43). Mucosal TNFalpha production was greater in relapsers compared with those who remained in remission. The levels of NF-kappaB in relapsers were significantly greater and levels of cytosolic IkappaBalpha were significantly lower compared with those measured in patients who remained in remission. CONCLUSIONS: These findings underscore the importance of incorporating biological parameters of inflammation in determining the clinical course of Crohn's disease.
BACKGROUND: The clinical course of Crohn's disease after the induction of remission with medical therapy is characterized by unpredictable relapse. AIM: To evaluate three surrogate markers, intestinal permeability, mucosal TNFalpha and nuclear factor (NF)-kappaB/IkappaBalpha expression, in order to determine the relationship of these parameters to clinical relapse. METHODS: Thirty patients with active Crohn's disease were treated with a 10 week course of prednisone using a tapering dosing regimen. Intestinal permeability (lactulose/mannitol [L/M ratio]) was determined at baseline and at the end of prednisone tapering. TNFalpha production and the levels of expression of NF-kappaB/IkappaBalpha were measured in colonic mucosal biopsies obtained after the induction of remission. RESULTS: Twenty-two patients (73%) achieved remission and 50% of patients experienced a clinical relapse during the ensuing 12 months. Treatment with prednisone resulted in a significant decrease in the L/M ratio. Of the patients that relapsed, 75% had a raised L/M ratio at the time of remission compared with 20% of patients with a normal L/M ratio (P < 0.008; hazard ratio = 6.094; CI 1.55, 17.43). Mucosal TNFalpha production was greater in relapsers compared with those who remained in remission. The levels of NF-kappaB in relapsers were significantly greater and levels of cytosolic IkappaBalpha were significantly lower compared with those measured in patients who remained in remission. CONCLUSIONS: These findings underscore the importance of incorporating biological parameters of inflammation in determining the clinical course of Crohn's disease.
Authors: Michel A Boivin; Dongmei Ye; John C Kennedy; Rana Al-Sadi; Chris Shepela; Thomas Y Ma Journal: Am J Physiol Gastrointest Liver Physiol Date: 2006-10-26 Impact factor: 4.052
Authors: Rana Al-Sadi; Moustafa Youssef; Manmeet Rawat; Shuhong Guo; Karol Dokladny; Mohammad Haque; Martin D Watterson; Thomas Y Ma Journal: Am J Physiol Gastrointest Liver Physiol Date: 2018-12-13 Impact factor: 4.052