Clinical Potential of Lactococcus lactis Mediated Delivery of Human Interleukin-10 and Trefoil Factors

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著者

    • REMAUT Erik
    • Department of Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University
    • BRAAT Henri
    • Department of Experimental Internal Medicine, Academic Medical Center
    • VANDENBROUCKE Klaas
    • Department of Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University
    • ROTTIERS Pieter
    • Department of Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University
    • STEIDLER Lothar
    • Department of Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University

抄録

Systemic treatment with infliximab, a monoclonal antibody that binds TNFα is among the most potent therapies for Crohn's disease. Despite initial successes with intravenous addition of IL-10, this treatment was abandoned in later trials. Both treatments suffered a serious drawback from the fact that they had to be administered systemically and thus caused potentially serious side effects. We used two mouse models for IBD to evaluate the efficacy of <i>L. lactis</i> mediated topical delivery of IL-10. In the Dextran Sulphate Sodium (DSS)-induced chronic colitis intragastric administration of mIL-10-secreting <i>L. lactis</i> led to a 50% reduction in inflammation. Also, daily administration of the engineered strain prevented the onset of colitis, normally associated with the IL-10 knockout genotype. In both models, the effect was strictly dependent on delivery of live bacteria. We engineered a strain exhibiting biological containment. To this end, the thymidilate synthase (<i>thy</i>A) gene of <i>L. lactis</i> was replaced with a synthetic human IL-10 gene. ThyA-deficient bacteria are suicidal in the absence of thymine or thymidine and therefore cannot accumulate in the environment. A limited clinical trail in Crohn's patients under physical containment proved that the treatment was safe, the biological containment strategy was effective and the results obtained suggested a clinical effect. In contrast to oral administration of purified protein, intragastric administration of Trefoil factor-secreting <i>L. lactis</i> was very effective in prevention and healing of acute DSS colitis. In addition this approach was successful in improving established chronic colitis in IL-10 knockout mice.<br>

収録刊行物

  • Bioscience and microflora  

    Bioscience and microflora 25(3), 81-97, 2006-07-01 

    JAPAN BIFIDUS FOUNDATION

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各種コード

  • NII論文ID(NAID)
    10018168584
  • NII書誌ID(NCID)
    AA1108739X
  • 本文言語コード
    ENG
  • 資料種別
    REV
  • ISSN
    13421441
  • データ提供元
    CJP書誌  J-STAGE 
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