Targeted adenovirus-induced expression of IL-10 decreases thymic apoptosis and improves survival in murine sepsis

Caroline Oberholzer, Andreas Oberholzer, Frances R. Bahjat, Rebecca M. Minter, Cynthia L. Tannahill, Amer Abouhamze, Drake LaFace, Beth Hutchins, Michael J. Clare-Salzler, Lyle L. Moldawer

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Abstract

Sepsis remains a significant clinical conundrum, and recent clinical trials with anticytokine therapies have produced disappointing results. Animal studies have suggested that increased lymphocyte apoptosis may contribute to sepsis-induced mortality. We report here that inhibition of thymocyte apoptosis by targeted adenovirus-induced thymic expression of human IL-10 reduced blood bacteremia and prevented mortality in sepsis. In contrast, systemic administration of an adenovirus expressing IL-10 was without any protective effect. Improvements in survival were associated with increases in Bcl-2 expression and reductions in caspase-3 activity and thymocyte apoptosis. These studies demonstrate that thymic apoptosis plays a critical role in the pathogenesis of sepsis and identifies a gene therapy approach for its therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)11503-11508
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number20
DOIs
StatePublished - Sep 25 2001

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Adenoviridae
Interleukin-10
Sepsis
Apoptosis
Survival
Thymocytes
Mortality
Bacteremia
Caspase 3
Genetic Therapy
Clinical Trials
Lymphocytes
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Targeted adenovirus-induced expression of IL-10 decreases thymic apoptosis and improves survival in murine sepsis. / Oberholzer, Caroline; Oberholzer, Andreas; Bahjat, Frances R.; Minter, Rebecca M.; Tannahill, Cynthia L.; Abouhamze, Amer; LaFace, Drake; Hutchins, Beth; Clare-Salzler, Michael J.; Moldawer, Lyle L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 20, 25.09.2001, p. 11503-11508.

Research output: Contribution to journalArticle

Oberholzer, C, Oberholzer, A, Bahjat, FR, Minter, RM, Tannahill, CL, Abouhamze, A, LaFace, D, Hutchins, B, Clare-Salzler, MJ & Moldawer, LL 2001, 'Targeted adenovirus-induced expression of IL-10 decreases thymic apoptosis and improves survival in murine sepsis', Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 20, pp. 11503-11508. https://doi.org/10.1073/pnas.181338198
Oberholzer, Caroline ; Oberholzer, Andreas ; Bahjat, Frances R. ; Minter, Rebecca M. ; Tannahill, Cynthia L. ; Abouhamze, Amer ; LaFace, Drake ; Hutchins, Beth ; Clare-Salzler, Michael J. ; Moldawer, Lyle L. / Targeted adenovirus-induced expression of IL-10 decreases thymic apoptosis and improves survival in murine sepsis. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 20. pp. 11503-11508.
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AU - LaFace, Drake

AU - Hutchins, Beth

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