Critical illness syndromes, such as acute respiratory distress syndrome (ARDS), septic shock, myocardial depression, and multiple organ failure all share the hypothesis that the host response plays a central pathogenic role. In this project, CCMD has established the infrastructure necessary to define these pathogenic host responses at the level of gene expression across thousands of mRNA transcripts, simultaneously. This technology will be used to create a large critical illness functional genomics database using in vitro models, small animal (rat and mouse) models, endotoxin-challenged volunteers, and ultimately critically ill patients. Preliminary work has identified more than 350 genes that are differentially regulated by the administration of endotoxin to healthy volunteers. Increasing bacterial doses in rats has shown that a number of genes are expressed in a grade manner that corresponds closely to infection severity.
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