Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biological Transport
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Colitis / immunology
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Colitis / pathology
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Colitis / prevention & control
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Colitis / therapy
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Colon / immunology
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Colon / metabolism
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Colon / microbiology
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Colon / pathology
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Dextran Sulfate
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Inflammatory Bowel Diseases / immunology
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Inflammatory Bowel Diseases / pathology
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Inflammatory Bowel Diseases / prevention & control
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Inflammatory Bowel Diseases / therapy*
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Interleukin-10 / administration & dosage*
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Interleukin-10 / biosynthesis*
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Interleukin-10 / genetics
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Interleukin-10 / metabolism
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Intestinal Mucosa / metabolism
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Intestinal Mucosa / pathology
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Lactococcus lactis / genetics*
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Lactococcus lactis / immunology
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Lactococcus lactis / metabolism*
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Mice
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Probiotics / therapeutic use*
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / metabolism
Substances
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Recombinant Proteins
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Interleukin-10
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Dextran Sulfate