title: Anti-tumor necrosis factor α prevents bowel fibrosis assessed by messenger RNA, histology, and magnetization transfer MRI in rats with Crohn's disease.
abstract: OBJECTIVE
  Treatment of Crohn's disease (CD) with anti-tumor necrosis factor α (TNFα) decreases intestinal inflammation, but the effect on fibrosis remains unclear. We hypothesized that treatment with rat-specific anti-TNFα will decrease the development of intestinal fibrosis in a rat model of CD. We further hypothesized that magnetization transfer magnetic resonance imaging (MT-MRI) will be sensitive in detecting these differences in collagen content.
  
  
  METHODS
  Rats were injected in the distal ileum and cecum with peptidoglycan-polysaccharide (PG-PS) or human serum albumin (control) at laparotomy and then received intraperitoneal injections of rat-specific anti-TNFα or vehicle daily for 21 days after laparotomy. Rats underwent MT-MRI abdominal imaging on day 19 or 20. MT ratio was calculated in the cecal wall. Cecal tissue histologic inflammation was scored. Cecal tissue procollagen, cytokine, and growth factor messenger RNAs were measured by quantitative real-time PCR.
  
  
  RESULTS
  PG-PS-injected rats treated with anti-TNFα had less histologic inflammation, and cecal tissue expressed lower levels of proinflammatory cytokine messenger RNAs than vehicle-treated PG-PS-injected rats (IL-1β: 5.59 ± 1.53 versus 10.41 ± 1.78, P = 0.02; IL-6: 23.23 ± 9.33 versus 45.89 ± 11.79, P = 0.07). PG-PS-injected rats treated with anti-TNFα developed less intestinal fibrosis than vehicle-treated PG-PS-injected rats by tissue procollagen I (2.87 ± 0.66 versus 9.28 ± 1.11; P = 0.00002), procollagen III (2.25 ± 0.35 versus 7.28 ± 0.76; P = 0.0000009), and MT-MRI (MT ratio: 17.79 ± 1.61 versus 27.95 ± 1.75; P = 0.0001). Insulin-like growth factor I (2.52 ± 0.44 versus 5.14 ± 0.60; P = 0.0007) and transforming growth factor β1 (2.34 ± 0.29 versus 3.45 ± 0.29; P = 0.006) were also decreased in anti-TNFα-treated PG-PS-injected rats.
  
  
  CONCLUSIONS
  Anti-TNFα prevents the development of bowel wall inflammation and fibrosis in the PG-PS rat model of CD. MT-MRI measurably demonstrates this decrease in intestinal fibrosis.
authors: Division of Gastroenterology, Department of Pediatrics and Communicable Diseases, University of Michigan Health System, Ann Arbor, MI 48109, USA. jeradler@umich.edu
authors: Jeremy
authors: J
authors: Adler
authors: Kinan
authors: K
authors: Rahal
authors: Scott D
authors: SD
authors: Swanson
authors: Phyllissa
authors: P
authors: Schmiedlin-Ren
authors: Ahren C
authors: AC
authors: Rittershaus
authors: Laura J
authors: LJ
authors: Reingold
authors: Josh S
authors: JS
authors: Brudi
authors: David
authors: D
authors: Shealy
authors: Ann
authors: A
authors: Cai
authors: Barbara J
authors: BJ
authors: McKenna
authors: Ellen M
authors: EM
authors: Zimmermann
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D003424:Crohn Disease / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007410:Intestinal Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D010457:Peptidoglycan / Q000633:toxicity; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011917:Rats, Inbred Lew; D060888:Real-Time Polymerase Chain Reaction; D012709:Serum Albumin / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D010457:Peptidoglycan; D011347:Procollagen; D012333:RNA, Messenger; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I