title: Small bowel fibrosis and systemic inflammatory response after ileocolonic anastomosis in IL-10 null mice.
abstract: BACKGROUND
  Crohn's disease recurrence after an ileocecal resection is common; yet, its pathophysiology is poorly understood and available treatment is suboptimal. The purpose of this study was to examine the bacterial, local, and systemic immune changes that follow ileocolonic anastomosis in a rodent model of Crohn's disease, the interleukin-10 gene-deficient (IL-10 null) mice.
  
  
  METHODS
  We divided wild-type and IL-10 null mice into three treatment groups: ileocolonic anastomosis, sham operation (ileo-ileal anastomosis), and control group without an operation. We sacrificed mice at 6 and 15 wks after the operation. At 6 wks, we assessed bacterial changes using the denaturing gel electrophoresis and similarity coefficient calculation. At both time points, we examined the small bowel for inflammation and fibrosis with histology. We measured the interferon gamma secretion by splenocytes stimulated with gastrointestinal bacterial antigens and splenocyte composition as a marker of systemic response.
  
  
  RESULTS
  At 6 wks, ileocolonic anastomosis resulted in increased similarity in bacterial species between the ileum and colon. The ileocolonic anastomosis did not lead to significant inflammation in the small intestine, but it resulted in an increased collagen deposition in all animals undergoing surgery, the most pronounced fibrosis of which was present in IL-10 null mice 15 wks after ileocolonic anastomosis. Furthermore, this was associated with significantly increased interferon gamma secretion by bacterial antigen-stimulated splenocytes and a decreased number of CD11+ cells in the same experimental group.
  
  
  CONCLUSIONS
  Ileocolonic anastomosis leads to bacterial changes in the terminal ileum. In the genetically susceptible host, it is associated with small bowel fibrosis and systemic immune alterations. The composition of immune cells in the spleen is altered and splenocytes hypersecrete proinflammatory cytokine (interferon gamma) when challenged with gastrointestinal bacterial antigens.
authors.affiliation: Department of Surgery, University of Alberta, 2-14A Zeidler Building, Edmonton, T6G 2X8 Alberta, Canada. amb1@ualberta.ca
authors.forename: Anna M
authors.initials: AM
authors.lastname: Borowiec
authors.forename: Beate C
authors.initials: BC
authors.lastname: Sydora
authors.forename: Jason
authors.initials: J
authors.lastname: Doyle
authors.forename: Le Luo
authors.initials: LL
authors.lastname: Guan
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Churchill
authors.forename: Karen
authors.initials: K
authors.lastname: Madsen
authors.forename: Richard N
authors.initials: RN
authors.lastname: Fedorak
mesh_terms: D000714:Anastomosis, Surgical / Q000379:methods; D000818:Animals; D003106:Colon / Q000276:immunology / Q000473:pathology / Q000601:surgery; D003424:Crohn Disease / Q000276:immunology / Q000473:pathology / Q000601:surgery; D004195:Disease Models, Animal; D004751:Enteritis / Q000276:immunology / Q000473:pathology / Q000601:surgery; D005355:Fibrosis / Q000473:pathology; D007082:Ileum / Q000276:immunology / Q000473:pathology / Q000601:surgery; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D011183:Postoperative Complications / Q000276:immunology / Q000473:pathology; D012008:Recurrence; D013154:Spleen / Q000276:immunology
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10; D007371:Interferon-gamma