Treatment of murine colitis by Lactococcus lactis secreting interleukin-10

Science. 2000 Aug 25;289(5483):1352-5. doi: 10.1126/science.289.5483.1352.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Colitis / immunology
  • Colitis / pathology
  • Colitis / prevention & control
  • Colitis / therapy
  • Colon / immunology
  • Colon / metabolism
  • Colon / microbiology
  • Colon / pathology
  • Dextran Sulfate
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / pathology
  • Inflammatory Bowel Diseases / prevention & control
  • Inflammatory Bowel Diseases / therapy*
  • Interleukin-10 / administration & dosage*
  • Interleukin-10 / biosynthesis*
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Lactococcus lactis / genetics*
  • Lactococcus lactis / immunology
  • Lactococcus lactis / metabolism*
  • Mice
  • Probiotics / therapeutic use*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism

Substances

  • Recombinant Proteins
  • Interleukin-10
  • Dextran Sulfate