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Interleukin-10 Knockout Mice Do Not Reliably Exhibit Macroscopic Inflammation: A Natural History Endoscopic Surveillance Study

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A Concise Commentary to this article was published on 17 March 2023

Abstract

Background

Interleukin (IL)-10 knockout (KO) mice, a model for inflammatory bowel disease (IBD), develop chronic enterocolitis due to an aberrant immune response to enteric antigens. Endoscopy, the gold standard for evaluation of human mucosal health, is not widely available for murine models.

Aims

To assess the natural history of left-sided colitis in IL-10 KO mice via serial endoscopies.

Methods

BALB/cJ IL-10 KO mice underwent regular endoscopic assessments from 2 up to 8 months of age. Procedures were recorded and blindly evaluated using a 4-component endoscopic score: mucosal wall transparency, intestinal bleeding, focal lesions and perianal lesions (0–3 points each). An endoscopic score ≥ 1 point was considered as the presence of colitis/flare.

Results

IL-10 KO mice (N = 40, 9 female) were assessed. Mean age at first endoscopy was 62.5 ± 2.5 days; average number of procedures per mouse was 6.0 ± 1.3. A total of 238 endoscopies were conducted every 24.8 ± 8.3 days, corresponding to 124.1 ± 45.2 days of surveillance per mouse. Thirty-three endoscopies in 24 mice (60%) detected colitis, mean endoscopy score 2.5 ± 1.3 (range: 1–6.3). Nineteen mice (47.5%) had one episode of colitis and 5 (12.5%) had 2–3 episodes. All exhibited complete spontaneous healing on subsequent endoscopies.

Conclusions

In this large-scale endoscopic surveillance study of IL-10 KO mice, 40% of mice did not develop endoscopic left-sided colitis. Furthermore, IL-10 KO mice did not exhibit persistent colitis and universally exhibited complete spontaneous healing without treatment. The natural history of colitis in IL-10 KO mice may not be comparable with that of IBD in humans and requires careful consideration.

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Acknowledgments

This study was supported in part by a grant to AR from the Kenneth Rainin Foundation.

Funding

This study was supported in part by a Grant to AR from the Kenneth Rainin Foundation.

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Authors

Contributions

MP and AR: conceived and designed the study. SYK, JHP, GL, and AR: performed the experiments. GL, AR and MP: analyzed the data. SYK, JHP, GL, and AR: wrote the manuscript, and AR and MP: revised and edited the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ali Rezaie.

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Kim, S.Y., Park, J.H., Leite, G. et al. Interleukin-10 Knockout Mice Do Not Reliably Exhibit Macroscopic Inflammation: A Natural History Endoscopic Surveillance Study. Dig Dis Sci 68, 1858–1862 (2023). https://doi.org/10.1007/s10620-023-07871-y

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