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Science 25 August 2000:
Vol. 289. no. 5483, pp. 1352 - 1355
DOI: 10.1126/science.289.5483.1352
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Reports

Treatment of Murine Colitis by Lactococcus lactis Secreting Interleukin-10

Lothar Steidler,1*dagger Wolfgang Hans,1dagger Lieven Schotte,1 Sabine Neirynck,1 Florian Obermeier,2 Werner Falk,2 Walter Fiers,1 Erik Remaut1

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.

1 Department of Molecular Biology, Ghent University and Flanders Interuniversity Institute for Biotechnology, K. L. Ledeganckstraat 35, 9000 Gent, Belgium.
2 Department of Internal Medicine I, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany.
*   To whom correspondence should be addressed. E-mail: lothar.steidler{at}dmb.rug.ac.be

dagger    These authors contributed equally to this work.

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Protective nutrients and functional foods for the gastrointestinal tract.
C. Duggan, J. Gannon, and W A. Walker (2002)
Am. J. Clinical Nutrition 75, 789-808
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Probiotics: a role in the treatment of intestinal infection and inflammation?.
E Isolauri, P V Kirjavainen, and S Salminen (2002)
Gut 50, iii54-59
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Immunoregulation in the gut: success and failures in human disease.
I Monteleone, P Vavassori, L Biancone, G Monteleone, and F Pallone (2002)
Gut 50, iii60-64
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New Cytokine Delivery System Using Gelatin Microspheres Containing Interleukin-10 for Experimental Inflammatory Bowel Disease.
H. Nakase, K. Okazaki, Y. Tabata, M. Ozeki, N. Watanabe, M. Ohana, S. Uose, K. Uchida, T. Nishi, M. Mastuura, et al. (2002)
J. Pharmacol. Exp. Ther. 301, 59-65
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Production and Targeting of the Brucella abortus Antigen L7/L12 in Lactococcus lactis: a First Step towards Food-Grade Live Vaccines against Brucellosis.
L. A. Ribeiro, V. Azevedo, Y. Le Loir, S. C. Oliveira, Y. Dieye, J.-C. Piard, A. Gruss, and P. Langella (2002)
Appl. Envir. Microbiol. 68, 910-916
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IL-10 therapy in Crohn's disease: at the crossroads.
H Herfarth and J Scholmerich (2002)
Gut 50, 146-147
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Multiple Levels of Activation of Murine CD8+ Intraepithelial Lymphocytes Defined by OX40 (CD134) Expression: Effects on Cell-Mediated Cytotoxicity, IFN-{gamma}, and IL-10 Regulation.
H.-C. Wang and J. R. Klein (2001)
J. Immunol. 167, 6717-6723
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Surface Expression of the Conserved C Repeat Region of Streptococcal M6 Protein within the Pip Bacteriophage Receptor of Lactococcus lactis.
B. L. Geller, N. Wade, T. D. Gilberts, D. E. Hruby, R. Johanson, and L. Topisirovic (2001)
Appl. Envir. Microbiol. 67, 5370-5376
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Inflammatory Mediators in Gastrointestinal Defense and Injury.
J. L. Wallace and L. Ma (2001)
Experimental Biology and Medicine 226, 1003-1015
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Molecular pathology of solid tumours: some practical suggestions for translating research into clinical practice.
I P M Tomlinson and M Ilyas (2001)
Mol. Pathol. 54, 203-205
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Design of a Protein-Targeting System for Lactic Acid Bacteria.
Y. Dieye, S. Usai, F. Clier, A. Gruss, and J.-C. Piard (2001)
J. Bacteriol. 183, 4157-4166
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The Prevention and Treatment of Murine Colitis Using Gene Therapy with Adenoviral Vectors Encoding IL-10.
J. O. Lindsay, C. J. Ciesielski, T. Scheinin, H. J. Hodgson, and F. M. Brennan (2001)
J. Immunol. 166, 7625-7633
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Commensal Host-Bacterial Relationships in the Gut.
L. V. Hooper and J. I. Gordon (2001)
Science 292, 1115-1118
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Complete DNA Sequence of Lactococcus lactis Adds Flavor to Genomics.
O. P. Kuipers (2001)
Genome Res. 11, 673-674
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The Ins and Outs of Body Surface Immunology.
A. Hayday and J. L. Viney (2000)
Science 290, 97-100
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Novel Anti-Inflammatory Approach to Treating Colitis.
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Journal Watch (General) 2000, 9
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The Complete Genome Sequence of the Lactic Acid Bacterium Lactococcus lactis ssp. lactis IL1403.
A. Bolotin, P. Wincker, S. Mauger, O. Jaillon, K. Malarme, J. Weissenbach, S. D. Ehrlich, and A. Sorokin (2001)
Genome Res. 11, 731-753
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