Interleukin 10 gene transfer prevents experimental colitis in rats

Background-The development of colitis in interleukin 10 (IL-10) deficient m ice, together with the known antiinflammatory and immunomodulatory properti es of this cytokine have prompted consideration of IL-10 as a treatment for inflammatory bowel disease (IBD). However, studies using hrIL-10 in IBD mo dels have yielded inconsistent results. Aims-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 nonrepli cating human type 5 adenovirus bearing the IL-10 gene, either 24 hours befo re 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 concentration s. 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 h istologically, and significantly reduced colonic myeloperoxidase activity a nd leukotriene B4 concentrations. In contrast, IL-10 gene transfer after th e 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.