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A genomic storm in critically injured humans

Author(s): Xiao, Wenzhong; Mindrinos, Michael N; Seok, Junhee; Cuschieri, Joseph; Cuenca, Alex G; et al

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Abstract: Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.
Publication Date: 19-Dec-2011
Electronic Publication Date: 21-Nov-2011
Citation: Xiao, Wenzhong, Mindrinos, Michael N, Seok, Junhee, Cuschieri, Joseph, Cuenca, Alex G, Gao, Hong, Hayden, Douglas L, Hennessy, Laura, Moore, Ernest E, Minei, Joseph P, Bankey, Paul E, Johnson, Jeffrey L, Sperry, Jason, Nathens, Avery B, Billiar, Timothy R, West, Michael A, Brownstein, Bernard H, Mason, Philip H, Baker, Henry V, Finnerty, Celeste C, Jeschke, Marc G, López, M Cecilia, Klein, Matthew B, Gamelli, Richard L, Gibran, Nicole S, Arnoldo, Brett, Xu, Weihong, Zhang, Yuping, Calvano, Steven E, McDonald-Smith, Grace P, Schoenfeld, David A, Storey, John D, Cobb, J Perren, Warren, H Shaw, Moldawer, Lyle L, Herndon, David N, Lowry, Stephen F, Maier, Ronald V, Davis, Ronald W, Tompkins, Ronald G. (2011). A genomic storm in critically injured humans. The Journal of Experimental Medicine, 208 (13), 2581 - 2590. doi:10.1084/jem.20111354
DOI: doi:10.1084/jem.20111354
ISSN: 0022-1007
EISSN: 1540-9538
Pages: 2581 - 2590
Type of Material: Journal Article
Journal/Proceeding Title: The Journal of Experimental Medicine
Version: Final published version. This is an open access article.

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