• C Oberholzer, A Oberholzer, F R Bahjat, R M Minter, C L Tannahill, A Abouhamze, D LaFace, B Hutchins, M J Clare-Salzler, and L L Moldawer.
• Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, USA.
• Proc. Natl. Acad. Sci. U.S.A. 2001 Sep 25; 98 (20): 11503-8.

AbstractSepsis 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.

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