Characterisation of enterocolitis in the piroxicam-accelerated interleukin-10 knock out mouse: a model mimicking inflammatory bowel disease

Kristine Holgersen; Peter Helding  Kvist; Helle Markholst; Axel Jacob Kornerup Hansen; Thomas Lindebo Holm

doi:10.1016/j.crohns.2013.08.002

Characterisation of enterocolitis in the piroxicam-accelerated interleukin-10 knock out mouse: a model mimicking inflammatory bowel disease

Kristine Holgersen, Peter Helding Kvist, Helle Markholst, Axel Jacob Kornerup Hansen, Thomas Lindebo Holm

Lifepharm

24 Citations (Scopus)

Abstract

Background: In inflammatory bowel disease a defective mucosal barrier, a dysregulated immune response and an excessive reactivity against the gut microbiota are assumed to cause a breakdown of the intestinal homeostasis and lead to chronic inflammation. Piroxicam treatment is a method for induction of colitis in IL-10 k.o. mice, which integrates a dysfunction of both the intestinal barrier and the immune system. However, the translational value of this model has not been thoroughly clarified. Aim: To characterise the piroxicam-accelerated colitis (PAC) IL-10 k.o. model with respect to clinical features, pathogenic mechanisms and its ability to respond to existing therapies. Methods: The PAC IL-10. k.o. model was established on a C57BL/6. J background and the clinical manifestations, immunological mechanisms and efficacy of ampicillin and anti-IL-12/23p40 treatment were assessed. Results: The PAC IL-10 k.o. mice developed weight loss and diarrhoea, and colonoscopy revealed a thickened granulomatous mucosa. Histological evaluation of ileum and colon showed Crohn's disease-like changes with pronounced hyperplasia and focal transmural inflammation. Ileitis was also observed in piroxicam treated wild type mice. The total number of neutrophils, monocytes and natural killer cells was elevated in the blood compared to IL-10 k.o. and wild type mice, indicating a role of the innate immune system in the pathogenesis. These findings were supported by analyses of the intestinal cytokine profile. Ampicillin and anti-IL-12/23p40 treatment significantly suppressed disease in the model. Conclusion: The PAC IL-10 k.o. model resembles several features of Crohn's disease and could be a useful in vivo model in preclinical research.

Original language	English
Journal	Journal of Crohn's and Colitis
Volume	8
Issue number	2
Pages (from-to)	147-160
Number of pages	14
ISSN	1873-9946
DOIs	https://doi.org/10.1016/j.crohns.2013.08.002
Publication status	Published - 1 Feb 2014

Keywords

Faculty of Health and Medical Sciences
Inflammatory bowel disease
Crohn's disease
Interleukin-10 knock out mouse
Piroxicam

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Characterisation of enterocolitis in the piroxicam-accelerated interleukin-10 knock out mouse : a model mimicking inflammatory bowel disease. / Holgersen, Kristine; Kvist, Peter Helding ; Markholst, Helle et al.

In: Journal of Crohn's and Colitis, Vol. 8, No. 2, 01.02.2014, p. 147-160.

Research output: Contribution to journal › Journal article › Research › peer-review

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title = "Characterisation of enterocolitis in the piroxicam-accelerated interleukin-10 knock out mouse: a model mimicking inflammatory bowel disease",

abstract = "Background: In inflammatory bowel disease a defective mucosal barrier, a dysregulated immune response and an excessive reactivity against the gut microbiota are assumed to cause a breakdown of the intestinal homeostasis and lead to chronic inflammation. Piroxicam treatment is a method for induction of colitis in IL-10 k.o. mice, which integrates a dysfunction of both the intestinal barrier and the immune system. However, the translational value of this model has not been thoroughly clarified. Aim: To characterise the piroxicam-accelerated colitis (PAC) IL-10 k.o. model with respect to clinical features, pathogenic mechanisms and its ability to respond to existing therapies. Methods: The PAC IL-10. k.o. model was established on a C57BL/6. J background and the clinical manifestations, immunological mechanisms and efficacy of ampicillin and anti-IL-12/23p40 treatment were assessed. Results: The PAC IL-10 k.o. mice developed weight loss and diarrhoea, and colonoscopy revealed a thickened granulomatous mucosa. Histological evaluation of ileum and colon showed Crohn's disease-like changes with pronounced hyperplasia and focal transmural inflammation. Ileitis was also observed in piroxicam treated wild type mice. The total number of neutrophils, monocytes and natural killer cells was elevated in the blood compared to IL-10 k.o. and wild type mice, indicating a role of the innate immune system in the pathogenesis. These findings were supported by analyses of the intestinal cytokine profile. Ampicillin and anti-IL-12/23p40 treatment significantly suppressed disease in the model. Conclusion: The PAC IL-10 k.o. model resembles several features of Crohn's disease and could be a useful in vivo model in preclinical research.",

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T2 - a model mimicking inflammatory bowel disease

AU - Holgersen, Kristine

AU - Kvist, Peter Helding

AU - Markholst, Helle

AU - Hansen, Axel Jacob Kornerup

AU - Holm, Thomas Lindebo

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Background: In inflammatory bowel disease a defective mucosal barrier, a dysregulated immune response and an excessive reactivity against the gut microbiota are assumed to cause a breakdown of the intestinal homeostasis and lead to chronic inflammation. Piroxicam treatment is a method for induction of colitis in IL-10 k.o. mice, which integrates a dysfunction of both the intestinal barrier and the immune system. However, the translational value of this model has not been thoroughly clarified. Aim: To characterise the piroxicam-accelerated colitis (PAC) IL-10 k.o. model with respect to clinical features, pathogenic mechanisms and its ability to respond to existing therapies. Methods: The PAC IL-10. k.o. model was established on a C57BL/6. J background and the clinical manifestations, immunological mechanisms and efficacy of ampicillin and anti-IL-12/23p40 treatment were assessed. Results: The PAC IL-10 k.o. mice developed weight loss and diarrhoea, and colonoscopy revealed a thickened granulomatous mucosa. Histological evaluation of ileum and colon showed Crohn's disease-like changes with pronounced hyperplasia and focal transmural inflammation. Ileitis was also observed in piroxicam treated wild type mice. The total number of neutrophils, monocytes and natural killer cells was elevated in the blood compared to IL-10 k.o. and wild type mice, indicating a role of the innate immune system in the pathogenesis. These findings were supported by analyses of the intestinal cytokine profile. Ampicillin and anti-IL-12/23p40 treatment significantly suppressed disease in the model. Conclusion: The PAC IL-10 k.o. model resembles several features of Crohn's disease and could be a useful in vivo model in preclinical research.

AB - Background: In inflammatory bowel disease a defective mucosal barrier, a dysregulated immune response and an excessive reactivity against the gut microbiota are assumed to cause a breakdown of the intestinal homeostasis and lead to chronic inflammation. Piroxicam treatment is a method for induction of colitis in IL-10 k.o. mice, which integrates a dysfunction of both the intestinal barrier and the immune system. However, the translational value of this model has not been thoroughly clarified. Aim: To characterise the piroxicam-accelerated colitis (PAC) IL-10 k.o. model with respect to clinical features, pathogenic mechanisms and its ability to respond to existing therapies. Methods: The PAC IL-10. k.o. model was established on a C57BL/6. J background and the clinical manifestations, immunological mechanisms and efficacy of ampicillin and anti-IL-12/23p40 treatment were assessed. Results: The PAC IL-10 k.o. mice developed weight loss and diarrhoea, and colonoscopy revealed a thickened granulomatous mucosa. Histological evaluation of ileum and colon showed Crohn's disease-like changes with pronounced hyperplasia and focal transmural inflammation. Ileitis was also observed in piroxicam treated wild type mice. The total number of neutrophils, monocytes and natural killer cells was elevated in the blood compared to IL-10 k.o. and wild type mice, indicating a role of the innate immune system in the pathogenesis. These findings were supported by analyses of the intestinal cytokine profile. Ampicillin and anti-IL-12/23p40 treatment significantly suppressed disease in the model. Conclusion: The PAC IL-10 k.o. model resembles several features of Crohn's disease and could be a useful in vivo model in preclinical research.

KW - Faculty of Health and Medical Sciences

KW - Inflammatory bowel disease

KW - Crohn's disease

KW - Interleukin-10 knock out mouse

KW - Piroxicam

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DO - 10.1016/j.crohns.2013.08.002

M3 - Journal article

C2 - 23994255

SN - 1873-9946

VL - 8

SP - 147

EP - 160

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

IS - 2

ER -

Characterisation of enterocolitis in the piroxicam-accelerated interleukin-10 knock out mouse: a model mimicking inflammatory bowel disease

Abstract

Keywords

UN SDGs

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