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 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.
Division of Internal Medicine C, Kaplan Medical Center, Rehovot, Israel.
Raia
R
Gratz
Stuart
S
Becker
Nadia
N
Sokolowski
Marcus
M
Schumann
David
D
Bass
Stephen D H
SD
Malnick
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000473:pathology; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10