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

2001; National Academy of Sciences; Volume: 98; Issue: 20 Linguagem: Inglês

10.1073/pnas.181338198

1091-6490

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

Adrenal Hormones and Disorders

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.