Colonoscopy and µPET/CT are valid techniques to monitor inflammation in the adoptive transfer colitis model in mice.

Abstract

BACKGROUND:

Preclinical in vivo research on inflammatory bowel diseases requires proper animal models and techniques allowing longitudinal monitoring of colonic inflammation without the need to kill animals. We evaluated colonoscopy and μ-positron emission tomography/computed tomography (μPET/CT) as monitoring tools in a model for chronic colitis in mice.

METHODS:

Colitis was induced by adoptive transfer of CD4(+)CD25(-)CD62L(+) T cells in immunocompromised severe combined immunodeficient mice. Three study protocols were designed. In study 1, colonoscopy and µPET/CT were performed once, 4 weeks after transfer. In study 2 and study 3, colitis was sequentially followed up through colonoscopy (study 2) or colonoscopy plus µPET/CT (study 3). Each study included postmortem evaluation of colonic inflammation (macroscopy, microscopy, and myeloperoxidase activity).

RESULTS:

In study 1, both colonoscopy and µPET/CT detected colitis 4 weeks after transfer. Study 2 showed a gradual increase in colonoscopic score from week 2 (1.4 ± 0.6) to week 8 (6.0 ± 1.1). In study 3, colitis was detected 2 weeks after transfer by µPET/CT (2.0 ± 0.4) but not by colonoscopy, whereas both techniques detected inflammation 4 and 6 weeks after transfer. Colonoscopy correlated with µPET/CT (r = 0.812, 0.884, and 0.781, respectively) and with postmortem analyses in all 3 studies.

CONCLUSIONS:

Adoptive transfer of CD4(+)CD25(-)CD62L(+) T cells in severe combined immunodeficient mice results in a moderate chronic colitis. Evolution of colitis could be monitored over time by both colonoscopy and µPET/CT. µPET/CT seems to detect inflammation at an earlier time point than colonoscopy. Both techniques represent reliable and safe methods without the need to kill animals.

• Authors: Marthe Heylen, Steven Deleye, Joris G De Man, Nathalie E Ruyssers, Wim Vermeulen, Sigrid Stroobants, Paul A Pelckmans, Tom G Moreels, Steven Staelens, Benedicte Y De Winter
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 19 Issue 5 Pg. 967-76 (Apr 2013) ISSN: 1536-4844 [Electronic] England
• PMID: 23407045 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peroxidase

Topics

• Adoptive Transfer
• Animals
• CD4-Positive T-Lymphocytes (immunology)
• Colitis (diagnosis, immunology)
• Colonoscopy
• Disease Models, Animal
• Female
• Inflammation (diagnosis, immunology)
• Mice
• Mice, Inbred BALB C
• Mice, SCID
• Peroxidase (metabolism)
• Positron-Emission Tomography
• Tomography, X-Ray Computed