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IL-10 Gene Therapy Is Therapeutic for Dextran Sodium Sulfate-Induced Murine Colitis

Digestive Diseases and Sciences volume 49, pages 1327–1334 (2004)Cite this article

Abstract

The transfer of genes encoding immunoregulatory proteins is a promising new strategy in the treatment of intestinal inflammation. Previous work has demonstrated that daily systemic interleukin (IL)-10 therapy is able to prevent disease onset in animal models of colitis but is not sufficient to treat established disease. This study investigates the therapeutic efficacy of an adenovirus encoding IL-10 (AdvmuIL-10) in the treatment of experimental colitis. Colitis was induced in BALB/c mice by the addition of dextran sodium sulfate to the drinking water for 7 days. A single systemic injection of AdvmuIL-10, empty cassette vector (Adv0), or saline vehicle was administered on day 4 after the onset of colitis. The addition of DSS to the drinking water led to an acute, dose-dependent colitis. A single injection of AdvmuIL-10 led to a marked reduction in both stool markers of inflammation (IL-1β, IL-6, and TNFRII) and serum IL-6. Furthermore, the histological colitis score was significantly reduced in mice receiving AdvmuIL-10 compared to controls (4.9 ± 1.1 Vs 9.1 ± 1.2, respectively; P<0.05). A single systemic injection of AdvmuIL-10 is therapeutic in mice with established DSS colitis. Gene therapy strategies using adenoviral vectors encoding IL-10 may prove to be a potent therapy for chronic inflammation of the colon such as Crohn's disease.

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Authors and Affiliations

  1. Department of Gastroenterology, St Marks Hospital, London, U.K.

    J. O. Lindsay

  2. Department of Histopathology, Charing Cross Hospital, London, U.K.

    A. Sandison & P. Cohen

  3. Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, London, U.K.

    F. M. Brennan

  4. Department of Hepatology, Royal Free and University College Medical School, Royal Free Campus, London, U.K

    H. J. F. Hodgson

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  1. J. O. Lindsay
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  2. A. Sandison
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  3. P. Cohen
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  4. F. M. Brennan
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  5. H. J. F. Hodgson
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Lindsay, J.O., Sandison, A., Cohen, P. et al. IL-10 Gene Therapy Is Therapeutic for Dextran Sodium Sulfate-Induced Murine Colitis. Dig Dis Sci 49, 1327–1334 (2004). https://doi.org/10.1023/B:DDAS.0000037830.22065.71

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  • DOI: https://doi.org/10.1023/B:DDAS.0000037830.22065.71

  • interleukin-10
  • gene therapy
  • colitis