Attenuated Salmonella typhimurium-mediated interleukin-10 delivery is beneficial for dextran sodium sulfate-induced murine colitis.

Abstract

Interleukin-10 is a potent immunoregulatory agent that appears to play a role in inflammatory bowel disease. We hypothesized that interleukin-10 delivery to the distal gastrointestinal tract using a unique delivery vehicle may serve as a novel therapeutic for the treatment of experimental colitis. A murine interleukin-10 cDNA was subcloned and transformed into attenuated Salmonella typhimurium. In vitro interleukin-10 production and biofunction were evaluated. This construct was then used against dextran sodium sulfate-induced murine colitis. A murine interleukin-10 producing S. typhimurium model was constructed. Enzyme linked immunosorbent assay and mast cell bioassay revealed interleukin-10 production. After single oral gavage feeding of 10 bacteria, persistence was noted within mesenteric lymph nodes at 6 weeks. Inoculation with/without the interleukin-10 plasmid (n = 7 per group) was performed before and after dextran sodium sulfate exposure. Postdextran sodium sulfate treatment revealed enhanced weight recovery in the S. typhimurium/interleukin-10 group compared to S. typhimurium/plasmid and phosphate buffered saline controls (P < 0.0001). The mean histology score for S. typhimurium/interleukin-10 was 0.86 compared to 3.14 and 3.17 for the S. typhimurium/plasmid and phosphate buffered saline controls respectively (P = 0.028). Attenuated S. typhimurium producing interleukin-10 can be successfully delivered to the murine gastrointestinal tract by single oral dosing. This novel delivery method improved recovery of chemically-induced murine colitis.