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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
Correspondence to: Dr S M Collins, Room 4W8, McMaster University Medical Centre, Hamilton, Ontario, Canada L8N 3Z5
Accepted for publication 9 September 1999
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.
AIMSTo examine the therapeutic
potential of overexpressing the IL-10 gene before and after the
induction of experimental colitis in rats.
METHODSGene 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.
RESULTSGene 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.
CONCLUSIONSGene therapy using an
adenovirus-IL-10 construct was successful in preventing but not in
reversing experimental colitis in the rat.
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