PMID- 23429466
OWN - NLM
STAT- MEDLINE
DCOM- 20130926
LR  - 20180913
IS  - 1536-4844 (Electronic)
IS  - 1078-0998 (Linking)
VI  - 19
IP  - 4
DP  - 2013 Mar-Apr
TI  - Anti-tumor necrosis factor alpha prevents bowel fibrosis assessed by messenger RNA, 
      histology, and magnetization transfer MRI in rats with Crohn's disease.
PG  - 683-90
LID - 10.1097/MIB.0b013e3182802c32 [doi]
AB  - OBJECTIVE: Treatment of Crohn's disease (CD) with anti-tumor necrosis factor alpha 
      (TNFalpha) decreases intestinal inflammation, but the effect on fibrosis remains 
      unclear. We hypothesized that treatment with rat-specific anti-TNFalpha 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-TNFalpha 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-TNFalpha had less histologic inflammation, and cecal tissue expressed lower 
      levels of proinflammatory cytokine messenger RNAs than vehicle-treated 
      PG-PS-injected rats (IL-1beta: 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-TNFalpha 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 beta1 
      (2.34 +/- 0.29 versus 3.45 +/- 0.29; P = 0.006) were also decreased in 
      anti-TNFalpha-treated PG-PS-injected rats. CONCLUSIONS: Anti-TNFalpha 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.
FAU - Adler, Jeremy
AU  - Adler J
AD  - Division of Gastroenterology, Department of Pediatrics and Communicable Diseases, 
      University of Michigan Health System, Ann Arbor, MI 48109, USA. 
      jeradler@umich.edu
FAU - Rahal, Kinan
AU  - Rahal K
FAU - Swanson, Scott D
AU  - Swanson SD
FAU - Schmiedlin-Ren, Phyllissa
AU  - Schmiedlin-Ren P
FAU - Rittershaus, Ahren C
AU  - Rittershaus AC
FAU - Reingold, Laura J
AU  - Reingold LJ
FAU - Brudi, Josh S
AU  - Brudi JS
FAU - Shealy, David
AU  - Shealy D
FAU - Cai, Ann
AU  - Cai A
FAU - McKenna, Barbara J
AU  - McKenna BJ
FAU - Zimmermann, Ellen M
AU  - Zimmermann EM
LA  - eng
GR  - 1R01DK073992/DK/NIDDK NIH HHS/United States
GR  - 5K12HD02882017/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Inflamm Bowel Dis
JT  - Inflammatory bowel diseases
JID - 9508162
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Peptidoglycan)
RN  - 0 (Procollagen)
RN  - 0 (RNA, Messenger)
RN  - 0 (Serum Albumin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Colitis/chemically induced/pathology/prevention & control
MH  - Crohn Disease/chemically induced/pathology/*prevention & control
MH  - Cytokines/genetics
MH  - Disease Models, Animal
MH  - Female
MH  - Fibrosis/chemically induced/pathology/*prevention & control
MH  - Humans
MH  - Inflammation/chemically induced/pathology/prevention & control
MH  - Insulin-Like Growth Factor I/genetics
MH  - Intestinal Diseases/chemically induced/pathology/*prevention & control
MH  - *Magnetic Resonance Imaging
MH  - Magnetics
MH  - Peptidoglycan/toxicity
MH  - Procollagen/genetics
MH  - RNA, Messenger/*genetics
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Real-Time Polymerase Chain Reaction
MH  - Serum Albumin/toxicity
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors
EDAT- 2013/02/23 06:00
MHDA- 2013/09/27 06:00
CRDT- 2013/02/23 06:00
PHST- 2013/02/23 06:00 [entrez]
PHST- 2013/02/23 06:00 [pubmed]
PHST- 2013/09/27 06:00 [medline]
AID - 10.1097/MIB.0b013e3182802c32 [doi]
PST - ppublish
SO  - Inflamm Bowel Dis. 2013 Mar-Apr;19(4):683-90. doi: 10.1097/MIB.0b013e3182802c32.