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IL-10 gene therapy prevents TNBS-induced colitis

Gene Therapy volume 9, pages 1715–1721 (2002)Cite this article

Abstract

The transfer of genes encoding immunomodulatory proteins to the intestinal mucosa is a promising new approach to the treatment of Crohn's disease (CD). This study investigates the therapeutic efficacy of an adenoviral vector encoding IL-10 (AdvmuIL-10) in experimental colitis. BALB/c mice were treated with a single intravenous injection of AdvmuIL-10, empty cassette virus (Adv0) or PBS prior to the induction of trinitrobenzene sulphonic acid (TNBS) colitis. AdvmuIL-10 treatment prevented the severe loss of body weight associated with TNBS administration. In addition, AdvmuIL-10 therapy led to a significant reduction in both stool markers of inflammation (IL-1β and TNFR-II) and acute phase response (serum amyloid protein). Finally, the histological scores of mice with TNBS colitis treated with AdvmuIL-10 were significantly lower than Adv0- or PBS-treated controls. The therapeutic efficacy of AdvmuIL-10 was associated with a decrease in the IFN-γ and IL-6 levels detected in colonic homogenates from mice with TNBS colitis, whereas no effect was observed on cytokine release from stimulated systemic lymphocytes. Thus, AdvmuIL-10 is an effective therapy in the TNBS model of colitis. Gene therapy strategies using adenoviral vectors encoding IL-10 may prove to be a potent therapy for chronic inflammatory conditions such as CD.

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Acknowledgements

We thank Joost Daalhuizen and Ingvild Kop for biotechnical assistance, and Professor FJW ten Kate for careful reading of the manuscript.

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  1. J Lindsay and C van Montfrans: The first two authors contributed equally to this work

Authors and Affiliations

  1. The Kennedy Institute of Rheumatology, Imperial College School of Medicine, London, UK

    J Lindsay & F Brennan

  2. Department of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands

    C van Montfrans, S van Deventer, A te Velde & M Sol Rodriguez Pena

  3. The Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands

    P Drillenburg

  4. The Department of Hepatology, Royal Free & University College Medical School, London, UK

    H Hodgson

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  1. J Lindsay
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  2. C van Montfrans
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Lindsay, J., van Montfrans, C., Brennan, F. et al. IL-10 gene therapy prevents TNBS-induced colitis. Gene Ther 9, 1715–1721 (2002). https://doi.org/10.1038/sj.gt.3301841

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