Interleukin 10 gene transfer prevents experimental colitis in rats.
BACKGROUND
The development of colitis in interleukin 10 (IL-10) deficient mice, together with the known anti-inflammatory and immunomodulatory properties of this cytokine have prompted consideration of IL-10 as a treatment for inflammatory bowel disease (IBD). However, studies using hrIL-10 in IBD models have yielded inconsistent results.


OBJECTIVE
To examine the therapeutic potential of overexpressing the IL-10 gene before and after the induction of experimental colitis in rats.


METHODS
Gene transfer was achieved by intraperitoneal injection of non-replicating human type 5 adenovirus bearing the IL-10 gene, either 24 hours before or one hour after intrarectal administration of dinitrobenzene sulphonic acid in rats. Colonic damage and inflammation was assessed macroscopically and by measuring myeloperoxidase activity and leukotriene B4 concentrations.


RESULTS
Gene transfer increased IL-10 protein in serum for up to six days. IL-10 gene transfer prior to colitis improved colitis macroscopically and histologically, and significantly reduced colonic myeloperoxidase activity and leukotriene B4 concentrations. In contrast, IL-10 gene transfer after the onset of colitis had no beneficial effect.


CONCLUSIONS
Gene therapy using an adenovirus-IL-10 construct was successful in preventing but not in reversing experimental colitis in the rat.
Barbara
G
G
The Intestinal Disease Research Program, Division of Gastroenterology, Departments of Medicine and Pathology, McMaster University Faculty of Health Sciences, Hamilton Health Sciences Corporation, Hamilton, Ontario, Canada.
Xing
Z
Z
Hogaboam
C M
CM
Gauldie
J
J
Collins
S M
SM
D000256:Adenoviridae; D000818:Animals; D003092:Colitis / Q000235:genetics / Q000628:therapy*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000627:therapeutic use; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms
D016753:Interleukin-10