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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Lan
Jinggang
J
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Warner
Thomas F
TF
Heise
Charles P
CP
D000284:Administration, Oral; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D016264:Dextran Sulfate; D041981:Gastrointestinal Tract / Q000382:microbiology; D005822:Genetic Vectors; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000096:biosynthesis; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D012486:Salmonella typhimurium / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism
D007155:Immunologic Factors; D016753:Interleukin-10; D016264:Dextran Sulfate