Murine monoclonal anti-TNF antibody administration has a beneficial effect on inflammatory bowel disease that develops in IL-10 knockout mice

Although the etiology of inflammatory bowel disease (IBD) is unknown, there is increasing evidence for the pivotal role played by tumor necrosis factor-alpha (TNF-alpha). Recent work has shown an increased concentration of TNF-alpha in both the bowel wall and in the stools of patients with IBD, and...

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Bibliographic Details
Published in:Digestive diseases and sciences 2002-08, Vol.47 (8), p.1723-1727
Main Authors: GRATZ, Raia, BECKER, Stuart, SOKOLOWSKI, Nadia, SCHUMANN, Marcus, BASS, David, MALNICK, Stephen D. H
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal - pharmacology
Biological and medical sciences
Digestive system
Disease Models, Animal
Inflammatory bowel disease
Inflammatory Bowel Diseases - etiology
Inflammatory Bowel Diseases - pathology
Injections, Intraperitoneal
Interleukin-10 - physiology
Investigative techniques, diagnostic techniques (general aspects)
Medical sciences
Mice
Mice, Knockout
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Tumor Necrosis Factor-alpha - immunology
Tumor Necrosis Factor-alpha - physiology
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Summary:Although the etiology of inflammatory bowel disease (IBD) is unknown, there is increasing evidence for the pivotal role played by tumor necrosis factor-alpha (TNF-alpha). Recent work has shown an increased concentration of TNF-alpha in both the bowel wall and in the stools of patients with IBD, and in children with that disease there are increased serum levels. Coincidental studies have shown that IL-10 knockout mice have increased levels of TNF-alpha and are known to develop a syndrome of stunted growth, anemia, bloody diarrhea, and colon tumors that mimics IBD. By injecting monoclonal antibodies intraperitoneally into IL-10 knockout mice, we were able to demonstrate significant histologic improvement of inflammation that correlates well with a resolution of diarrhea and rectal bleeding. This finding is consistent with a role for anti-TNF-alpha in the pathogenesis of IBD and suggests that this model may be of use for examining the effects of anti-TNF-alpha antibody administration.
ISSN:0163-2116
1573-2568
DOI:10.1023/A:1016476024293