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A genomic storm in critically injured humans

Authors :
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.
Source :
The Journal of Experimental Medicine; December 2011, Vol. 208 Issue: 13 p2581-2590, 10p
Publication Year :
2011

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.

Details

Language :
English
ISSN :
00221007 and 15409538
Volume :
208
Issue :
13
Database :
Supplemental Index
Journal :
The Journal of Experimental Medicine
Publication Type :
Periodical
Accession number :
ejs57382133
Full Text :
https://doi.org/10.1084/jem.20111354