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Dose-dependent improvements in outcome with adenoviral expression of interleukin-10 in a murine model of multisystem organ failure

Gene Therapy volume 13, pages 276–282 (2006)Cite this article

Abstract

Targeted expression of interleukin-10 (IL-10) has been proposed as a means to suppress acute and chronic inflammation. We explored the capacity of targeted adenoviral expression of human or viral IL-10 to improve outcome in a zymosan-induced model of acute lung injury and multisystem organ failure. Intratracheal administration of adenovirus expressing either human or viral IL-10 prior to zymosan administration significantly improved survival at a dose of 107 particles (P<0.01), whereas the same recombinant vectors were ineffective at 108 particles and increased mortality at 109 particles. Improved survival after administration of 107 particles of adenovirus expressing viral or human IL-10 was associated with local tissue expression of IL-10 (100–300 pg/g wet wt). In contrast, mortality after administration of 109 particles was associated with markedly elevated IL-10 expression, both in the lung (10 000–70 000 pg/g wet wt) and systemically (1000–3000 pg/ml plasma), with evidence of an exaggerated systemic inflammatory response (plasma IL-6 and TNFα). Targeted gene expression of IL-10 can be used to treat acute inflammatory processes, but increased doses resulting in its systemic release are not associated with improvements in outcome, and may actually exacerbate acute inflammatory processes.

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Acknowledgements

This work was supported in part by Grants R01 GM-63021-03, awarded by the National Institute of General Medical Sciences. PM and PE were supported by a training Grant T32 GM-08235-05, in burns and trauma research.

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Author notes

  1. P F McAuliffe and M E Murday: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA

    P F McAuliffe, M E Murday, P A Efron, P O Scumpia, R Ungaro, Amer Abouhamze, C L Tannahill & L L Moldawer

  2. Canji Inc., San Diego, CA, USA

    B Hutchins & D LaFace

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  1. P F McAuliffe
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  2. M E Murday
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Correspondence to L L Moldawer.

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McAuliffe, P., Murday, M., Efron, P. et al. Dose-dependent improvements in outcome with adenoviral expression of interleukin-10 in a murine model of multisystem organ failure. Gene Ther 13, 276–282 (2006). https://doi.org/10.1038/sj.gt.3302600

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