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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98 Scopus citations

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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    Oberholzer, C., Oberholzer, A., Bahjat, F. R., Minter, R. M., Tannahill, C. L., Abouhamze, A., LaFace, D., Hutchins, B., Clare-Salzler, M. J., & Moldawer, L. L. (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, 98(20), 11503-11508. https://doi.org/10.1073/pnas.181338198