Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Inflammation Enhances Resection-Induced Intestinal Adaptive Growth in IL-10 Null Mice
AU - Speck, Karen E.
AU - Garrison, Aaron P.
AU - Rigby, Rachael J.
AU - von Allmen, Doug C.
AU - Lund, P. Kay
AU - Helmrath, Michael A.
PY - 2011/6/1
Y1 - 2011/6/1
N2 - Background. Surgical resection of the ileum, cecum, and proximal right colon (ICR) is common in the management of Crohn's disease, yet little is known about the effect of active inflammation on the adaptive response following intestinal loss. We recently developed a surgical model of ICR in germ-free (GF) IL-10 null mice that develop small intestinal inflammation only when mice undergo conventionalization with normal fecal microflora (CONV) before surgical intervention. In this study, we examined the effects of postsurgical small bowel inflammation on adaptive growth after ICR. Methods. GF 129SvEv IL-10 null mice, 8-10 wk old, were allocated to GF or CONV groups. Nonoperated GF and CONV mice provided baseline controls. Two wk later, GF and CONV mice were further allocated to ICR or sham operation. Small intestine and colon were harvested 7 d after surgery for histological analysis. Results. All mice within the gnotobiotic facility maintained GF status and did not develop small intestinal or colonic inflammation. CONV resulted in colitis in all groups, whereas small intestinal inflammation was only observed following ICR. Resection-induced small intestinal inflammation in CONV mice was associated with increases in proliferation, crypt depth, and villus height compared with GF mice after ICR. Resection-induced increases in crypt fission only occurred in CONV mice. Conclusion. ICR-dependent small intestinal inflammation in CONVIL-10 null mice dramatically enhances early adaptive growth of the small intestine. Additional studies utilizing our model may provide clinical insight leading to optimal therapies in managing IBD patients after surgical resection.
AB - Background. Surgical resection of the ileum, cecum, and proximal right colon (ICR) is common in the management of Crohn's disease, yet little is known about the effect of active inflammation on the adaptive response following intestinal loss. We recently developed a surgical model of ICR in germ-free (GF) IL-10 null mice that develop small intestinal inflammation only when mice undergo conventionalization with normal fecal microflora (CONV) before surgical intervention. In this study, we examined the effects of postsurgical small bowel inflammation on adaptive growth after ICR. Methods. GF 129SvEv IL-10 null mice, 8-10 wk old, were allocated to GF or CONV groups. Nonoperated GF and CONV mice provided baseline controls. Two wk later, GF and CONV mice were further allocated to ICR or sham operation. Small intestine and colon were harvested 7 d after surgery for histological analysis. Results. All mice within the gnotobiotic facility maintained GF status and did not develop small intestinal or colonic inflammation. CONV resulted in colitis in all groups, whereas small intestinal inflammation was only observed following ICR. Resection-induced small intestinal inflammation in CONV mice was associated with increases in proliferation, crypt depth, and villus height compared with GF mice after ICR. Resection-induced increases in crypt fission only occurred in CONV mice. Conclusion. ICR-dependent small intestinal inflammation in CONVIL-10 null mice dramatically enhances early adaptive growth of the small intestine. Additional studies utilizing our model may provide clinical insight leading to optimal therapies in managing IBD patients after surgical resection.
KW - IL-10 null
KW - inflammatory bowel disease
KW - IBD
KW - ileocecal resection
KW - ICR
KW - adaptation
KW - crypt fission
KW - proliferation
KW - microbial effect
KW - conventionalization
KW - SMALL-BOWEL RESECTION
KW - POSTOPERATIVE CROHNS-DISEASE
KW - ILEOCECAL RESECTION
KW - INTERLEUKIN-10-DEFICIENT MICE
KW - STEM-CELLS
KW - ADAPTATION
KW - COLITIS
KW - MODELS
KW - ADENOCARCINOMA
KW - PROLIFERATION
UR - http://www.scopus.com/inward/record.url?scp=79955623508&partnerID=8YFLogxK
U2 - 10.1016/j.jss.2009.09.051
DO - 10.1016/j.jss.2009.09.051
M3 - Journal article
VL - 168
SP - 62
EP - 69
JO - Journal of Surgical Research
JF - Journal of Surgical Research
SN - 0022-4804
IS - 1
ER -