Targeted adenovirus-induced expression of IL-10 decreases thymic apoptosis and improves survival in murine sepsis
AUTOR(ES)
Oberholzer, Caroline
FONTE
The National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=58759Documentos Relacionados
- Requirement of BAX for Efficient Adenovirus-Induced Apoptosis
- Adenovirus-induced inhibition of cellular DNase.
- Adenovirus-induced mutations at the hypoxanthine phosphoribosyltransferase locus of Chinese hamster cells.
- IL-10 down-regulates the expression of survival associated gene hspX of Mycobacterium tuberculosis in murine macrophage
- Redox Regulation of Adenovirus-Induced AP-1 Activation by Overexpression of Manganese-Containing Superoxide Dismutase
