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

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

Research output: Contribution to journalArticle

96 Citations (Scopus)

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
Externally publishedYes

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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

  • Genetics
  • 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; 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, F, 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 ; 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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