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Experimental Intestinal Stenosis Alters Crohn’s Disease-Like Intestinal Inflammation in Ileitis-Prone Mice

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An Editorial to this article was published on 04 August 2021

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.

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Acknowledgments

Τhe authors are grateful to professor George Kollias and his colleagues Vasiliki Koliaraki, Michalis Meletiou and Vasileios Ntafis for sharing their experience, facilities and equipment whenever needed for this study. We also thank the veterinarian Dr Ioannis Chaniotakis for his academic input and technical assistance throughout the study.

Funding

No specific funding has been received for this study.

Author information

Authors and Affiliations

  1. Department of Pediatric Surgery, ‘Agia Sofia’ Children’s Hospital, Thivon and Papadiamantopoulou Street, 11527, Athens, Greece

    Ioannis Georgopoulos & Eleftheria Mavrigiannaki

  2. Department of Pathology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Sotiria Stasinopoulou & Dina Tiniakos

  3. 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Georgios Renieris

  4. Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Medical School Brandenburg Theodor Fontane, Dessau, Germany

    Georgios Nikolakis

  5. Gastrointestinal Unit, 3rd Department of Internal Medicine, Sotiria Hospital, National and Kapodistrian University of Athens, Athens, Greece

    Giorgos Bamias

  6. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK

    Dina Tiniakos

  7. 2nd Department of Surgery, Aretaieion University Hospital, Medical School, National and Kapodistrian University of Athens, Vasilissis Sofias Ave. 76, 11528, Athens, Greece

    Ioannis Papaconstantinou

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  1. Ioannis Georgopoulos
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Contributions

IG: corresponding author, study design, project development, experiments execution, data collection and analysis, manuscript writing. EM: experiments support and execution, data collection and analysis, manuscript writing and editing. SS: histopathologic evaluation, data analysis and interpretation, manuscript editing. GR: data analysis and interpretation, manuscript writing and editing, statistical analysis. GN: data analysis and interpretation, manuscript editing. GB: data interpretation, manuscript writing and editing. DT: histopathologic evaluation, data analysis and interpretation, manuscript editing. IP: project supervision, study conception and design, manuscript editing. All authors critically revised the manuscript for intellectual content and approved the submitted final version.

Corresponding author

Correspondence to Ioannis Georgopoulos.

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All authors declare that they have no conflicts of interest.

Ethics statement

Animal housing and experiments were performed in the animal facilities of the Laboratory of Experimental Surgery and Surgery Research "N.S. Christeas" of the National and Kapodistrian University of Athens (code of the facility EL 25 BIO 05). The study, during all stages, was in compliance with the Presidential Degree 56/2013 [19] which incorporates the EU Directive 2010/63/EU for animal experiments [18] and the Greek law 2015/2001, on the protection of animals used for scientific purposes. Ethical approval was granted by the Ethical Committee of Areteion Univeristy Hospital of National and Kapodistrian University of Athens (No B-154/04-02-2016) and the Department of Agricultural and Veterinary Policy of the Region of Attica of the Hellenic Democracy (No 599017/04-10-19).

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Georgopoulos, I., Mavrigiannaki, E., Stasinopoulou, S. et al. Experimental Intestinal Stenosis Alters Crohn’s Disease-Like Intestinal Inflammation in Ileitis-Prone Mice. Dig Dis Sci 67, 1783–1793 (2022). https://doi.org/10.1007/s10620-021-07161-5

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