TY - JOUR
T1 - Characterisation of enterocolitis in the piroxicam-accelerated interleukin-10 knock out mouse
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
U2 - 10.1016/j.crohns.2013.08.002
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 -
