Ioannis Georgopoulos1, Eleftheria Mavrigiannaki2, Sotiria Stasinopoulou3, Georgios Renieris4, Georgios Nikolakis5, Giorgos Bamias6, Dina Tiniakos3,7, Ioannis Papaconstantinou8. 1. Department of Pediatric Surgery, 'Agia Sofia' Children's Hospital, Thivon and Papadiamantopoulou Street, 11527, Athens, Greece. ioannis.georgopoulos@med.uoa.gr. 2. Department of Pediatric Surgery, 'Agia Sofia' Children's Hospital, Thivon and Papadiamantopoulou Street, 11527, Athens, Greece. 3. Department of Pathology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 4. 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 5. Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Medical School Brandenburg Theodor Fontane, Dessau, Germany. 6. Gastrointestinal Unit, 3rd Department of Internal Medicine, Sotiria Hospital, National and Kapodistrian University of Athens, Athens, Greece. 7. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. 8. 2nd Department of Surgery, Aretaieion University Hospital, Medical School, National and Kapodistrian University of Athens, Vasilissis Sofias Ave. 76, 11528, Athens, Greece.
Abstract
BACKGROUND: Clinical observations indicate that mechanical factors contribute to the expression or recurrence of Crohn's disease. We investigated whether the creation of an intestinal stenosis could alter the severity of the expected Crohn-like ileitis, in a Crohn's disease animal model, the TNFΔare/+ mouse. METHODS: Thirty-six, 6-weeks-old TNFΔare/+ mice, were divided into 3 intervention groups: triple suture, single suture and sham. In the terminal ileum, in the first group, a triple suture stenosis was created, whereas, in the second, a loose suture was placed. Same triple-suture stenosis was performed on twelve wild type mice. All animals were sacrificed at 6 weeks post-operatively and the ileum parts were evaluated histopathologically. A summative total ileitis score was applied in each sample using a bespoke semiquantitative histological scoring system for the Crohn-like changes. RESULTS: The triple suture stenosis induced significant muscular hypertrophy proximal to interventional site which was more prominent in TNFΔare/+ than wild type mice. In triple suture group, the total ileitis score was significantly increased proximal to the intervention as compared to the single suture (P: 0.004) and the sham groups (P: 0.013). The total ileitis score distally, was unaffected, regardless of the experimental intervention. Intestinal stenosis did not induce intestinal inflammation in wild type mice. CONCLUSION: The creation of a stenosis in the terminal ileum of TNFΔare/+ mice alters Crohn-like inflammation. We assume that mechanical forces, such as intraluminal pressure, may contribute as important co-factors to the pathophysiology of Crohn's disease in genetically predisposed subjects.
BACKGROUND: Clinical observations indicate that mechanical factors contribute to the expression or recurrence of Crohn's disease. We investigated whether the creation of an intestinal stenosis could alter the severity of the expected Crohn-like ileitis, in a Crohn's disease animal model, the TNFΔare/+ mouse. METHODS: Thirty-six, 6-weeks-old TNFΔare/+ mice, were divided into 3 intervention groups: triple suture, single suture and sham. In the terminal ileum, in the first group, a triple suture stenosis was created, whereas, in the second, a loose suture was placed. Same triple-suture stenosis was performed on twelve wild type mice. All animals were sacrificed at 6 weeks post-operatively and the ileum parts were evaluated histopathologically. A summative total ileitis score was applied in each sample using a bespoke semiquantitative histological scoring system for the Crohn-like changes. RESULTS: The triple suture stenosis induced significant muscular hypertrophy proximal to interventional site which was more prominent in TNFΔare/+ than wild type mice. In triple suture group, the total ileitis score was significantly increased proximal to the intervention as compared to the single suture (P: 0.004) and the sham groups (P: 0.013). The total ileitis score distally, was unaffected, regardless of the experimental intervention. Intestinal stenosis did not induce intestinal inflammation in wild type mice. CONCLUSION: The creation of a stenosis in the terminal ileum of TNFΔare/+ mice alters Crohn-like inflammation. We assume that mechanical forces, such as intraluminal pressure, may contribute as important co-factors to the pathophysiology of Crohn's disease in genetically predisposed subjects.