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Poster presentations: Basic Science 2020

P054 The impact of intestinal stenosis on the expression of Crohn’s disease in young mice with genetic predisposition

I. Georgopoulos1, E. Mavrigiannaki1, S. Stasinopoulou2, G. Renieris3, G. NIkolakis4, G. Kollias5, D. Tiniakos6, I. Papaconstantinou7

1’Agia Sofia’ Children’s Hospital of Athens, Department of Surgery, Athens, Greece, 2417 Veterans Administration Hospital NIMTS, Department of Pathology, Athens, Greece, 3National and Kapodistrian University of Athens, Medical School, 4th Department of Internal Medicine, Athens, Greece, 4Dessau Medical Center, Medical School Brandenburg Theodor Fontane, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau, Germany, 5National and Kapodistrian University of Athens, Medical School, Department of Physiology, Athens, Greece, 6Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Department of Pathology, Athens, Greece, 7National and Kapodistrian University of Athens, Medical School, Aretaieion University Hospital, Second Department of Surgery, Athens, Greece

Background

In the majority of patients, the areas of the intestine affected in Crohn’s disease (CD) are the terminal ileum and less commonly the rectum. The terminal ileum is affected in the majority of genetic animal models of CD as well. Additionally, CD recurs at sites of tight anastomosis or strictures postoperatively. These observations lead to the assumption that increased intraluminal pressure related to the presence of a valve, sphincter or stenosis is associated with CD pathogenesis. We investigated the hypothesis that the creation of a partial intestinal stenosis could have an impact on disease severity, in a genetic animal model of CD (TNFΔare/+). TNFΔare/+ mice overexpress TNFα leading to a Crohn-like colitis in the terminal ileum.

Methods

Twenty-nine TNFΔare/+ mice, 6 weeks old, were divided into three intervention groups: stenosis, sham and control. In the stenosis group (n = 11), a partial small bowel obstruction was created via a novel triple suture technique, approximately 3 cm from the ileocecal valve. In the control group (n = 9), a loose single suture was placed at the aforementioned site to test the direct effect of the foreign material on the intestinal wall. The sham group (n = 9) received a sham operation. The triple suture stenosis was also performed on wild-type (WT) C57BL/6 mice (group WT, n = 9). 6 weeks post-surgery all animals were sacrificed and samples from the ileum 3 cm proximal and 3 cm distal to the intervention site were collected for histopathological evaluation. The Crohn-like changes were assessed using a modified colitis histological scoring system (based on Katakura et al., JCI 2005; 115: 695–702).

Results

Proximal to the intervention, the mean colitis score of stenosis group (10.18 ± 0.87) was significantly higher compared with sham (6.33 ± 0.97, p: 0.009) and control group (5.00 ± 0.91, p: 0.001). There was no difference between sham and control group (p: 0.332). No significant differences between the groups were reported distal to the intervention. The triple suture technique led to Crohn-like inflammatory lesions only in the TNFΔare/+ mice, as shown from the significantly increased score compared with WT mice proximal and distal to the stenosis (10.18 ± 0.87 vs. 0.67 ± 0.37, p < 0.001 and 9.20 ± 1.09 vs. 0.33 ± 0.24, p < 0.001).

Conclusion

The creation of a stenotic segment in the intestine of TNFΔare/+ mice, led to higher colitis score than expected. The probable mechanism is the increased intraluminal pressure proximal to the stenosis. This suggests that mechanical forces contribute as important co-factors in the pathophysiology of CD, in genetically predisposed populations.