Document Detail

Tumor necrosis factor inhibitor ameliorates murine intestinal graft-versus-host disease.
MedLine Citation:
PMID:  10029618     Owner:  NLM     Status:  MEDLINE    
BACKGROUND & AIMS: Transfer of T helper cells from DBA/2 mice to irradiated allogeneic B6D2F1 mice leads to development of colonic graft-versus-host disease with pathological features of inflammatory bowel disease. To examine the role of tumor necrosis factor (TNF) in graft-versus-host disease enteropathy, an adenoviral vector encoding a TNF inhibitor protein was administered. METHODS: Irradiated B6D2F1 mice were infused with DBA/2 bone marrow and spleen cells. Mice then received either a control beta-galactosidase-encoding adenovirus or an adenovirus encoding a TNF inhibitor, composed of the extracellular domain of the human 55-kilodalton TNF receptor linked to the murine immunoglobulin G1 heavy chain. Mucosal permeability to sucralose and colonic histology were assessed 14 and 25 days after transplantation. RESULTS: Less diarrhea was observed in DBA/2 --> B6D2F1 mice expressing the TNF inhibitor, and colonic sections from these mice had significantly less inflammation and epithelial cell abnormalities. In TNF inhibitor recipients, mucosal permeability to sucralose was similar to that in nonirradiated control mice and significantly less than in recipients of the control adenovirus. CONCLUSIONS: TNF inhibition decreases the severity of enteropathy in the DBA/2 --> B6D2F1 murine model of colonic graft-versus-host disease.
G R Brown; G Lindberg; J Meddings; M Silva; B Beutler; D Thiele
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Gastroenterology     Volume:  116     ISSN:  0016-5085     ISO Abbreviation:  Gastroenterology     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-03-22     Completed Date:  1999-03-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  593-601     Citation Subset:  AIM; IM    
Liver Unit, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, 75235-9151, USA.
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MeSH Terms
Bone Marrow Transplantation*
Colon / physiology,  transplantation*
Graft vs Host Disease / therapy*
Immunoglobulin G / biosynthesis,  genetics
Immunoglobulin Heavy Chains / biosynthesis,  genetics
Immunosuppression / methods
Lymphocyte Transfusion*
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Inbred Strains
Receptors, Tumor Necrosis Factor / biosynthesis*,  genetics
Recombinant Fusion Proteins / biosynthesis
Spleen / immunology
Sucrose / analogs & derivatives,  metabolism
T-Lymphocytes, Helper-Inducer / transplantation*
Transplantation, Homologous / immunology*
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
Whole-Body Irradiation
beta-Galactosidase / biosynthesis,  genetics
Grant Support
Reg. No./Substance:
0/Immunoglobulin G; 0/Immunoglobulin Heavy Chains; 0/Receptors, Tumor Necrosis Factor; 0/Recombinant Fusion Proteins; 0/Tumor Necrosis Factor-alpha; 56038-13-2/trichlorosucrose; 57-50-1/Sucrose; EC

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