Treatment of murine colitis by Lactococcus lactis secreting interleukin-10.
The cytokine interleukin-10 (IL-10) has shown promise in clinical trials for treatment of inflammatory bowel disease (IBD). Using two mouse models, we show that the therapeutic dose of IL-10 can be reduced by localized delivery of a bacterium genetically engineered to secrete the cytokine. Intragastric administration of IL-10-secreting Lactococcus lactis caused a 50% reduction in colitis in mice treated with dextran sulfate sodium and prevented the onset of colitis in IL-10(-/-) mice. This approach may lead to better methods for cost-effective and long-term management of IBD in humans.
Steidler
L
L
Department of Molecular Biology, Ghent University and Flanders Interuniversity Institute for Biotechnology, K. L. Ledeganckstraat 35, 9000 Gent, Belgium. lothar.steidler@dmb.rug.ac.be
Hans
W
W
Schotte
L
L
Neirynck
S
S
Obermeier
F
F
Falk
W
W
Fiers
W
W
Remaut
E
E
D000818:Animals; D001692:Biological Transport; D003092:Colitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control / Q000628:therapy; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016264:Dextran Sulfate; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D013294:Lactococcus lactis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D019936:Probiotics / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000378:metabolism
D011994:Recombinant Proteins; D016753:Interleukin-10; D016264:Dextran Sulfate