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  • Acquired Diseases
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Interleukin-10 produced by recombinant adenovirus prolongs survival of cardiac allografts in rats

Gene Therapy volume 7, pages 505–510 (2000)Cite this article

Abstract

Interleukin-10 (IL-10) and interleukin-4 (IL-4), two Th2-derived cytokines, are molecules with anti-inflammatory and immunodeviating properties whose direct expression in allografts may prolong graft survival. Recombinant adenoviruses represent efficient vectors for gene tranfer in quiescent cells in vivo. Adenoviral vectors encoding rat IL-10 (AdIL-10), rat IL-4 (AdIL-4) or β-galactosidase (AdlacZ) or without transgene (Addl324) were injected directly into rat hearts at the time of transplantation in order to test their potential to prolong heart allograft survival. Expression of vectorized sequences was confirmed in heart biopsies, and kinetic analysis of β-galactosidase showed transient expression. Cardiac allograft survival was significantly prolonged after administration of 109 p.f.u. of AdIL-10 (16.6 ± 3.2 days, P < 0.05), but not adil-4 (9.8 ± 1.6 days), compared with addl324-treated (9.3 ± 3.3 days) or untreated groups (7.8 ± 1.5 days). immunohistochemical analysis of allografts after gene transfer of il-10 showed that leukocyte infiltration was quantitatively equivalent to that seen in control groups but with a strong tendency towards lower levels of cd8+ cells. Importantly, adenovirus-derived IL-10 modified the functional status of leukocytes by inducing a significant decrease in IFN-γ production but significantly increased transforming-growth factor β1 (TGF-β1) expression within the grafts compared with those treated with Addl324. These results show that expression of IL-10 by rat hearts after gene transfer mediated by an adenoviral vector decreases allogeneic immune responses and allows prolongation of allograft survival.

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Acknowledgements

We are grateful to Valia Proust, Helga Smit and Claire Usal for performing heart transplantations and to researchers that contributed with reagents. This work was financed in part by the Association pour la Recherche sur le Cancer and the Fondation Transvie and European Union grant Biomed2 BMM-CT98–3277.

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  1. A David

    Present address: Molecular Medicine and Gene Therapy Unit, University of Manchester, Manchester, M13 9PT, UK

  2. A David and J Chétritt: The first two authors contributed equally to this work

Authors and Affiliations

  1. Institut National de la Santé Et de la Recherche Médicale (INSERM) U437 and Institut de Transplantation et de Recherche en Transplantation, Nantes, France

    A David, J Chétritt, C Guillot, L Tesson, J-M Heslan, M-C Cuturi, J-P Soulillou & I Anegon

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David, A., Chétritt, J., Guillot, C. et al. Interleukin-10 produced by recombinant adenovirus prolongs survival of cardiac allografts in rats. Gene Ther 7, 505–510 (2000). https://doi.org/10.1038/sj.gt.3301114

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