A genomic storm in critically injured humans
Wenzhong Xiao,Wenzhong Xiao,Michael N. Mindrinos,Junhee Seok,Joseph Cuschieri,Alex G. Cuenca,Hong Gao,Douglas L. Hayden,Laura Hennessy,Ernest E. Moore,Joseph P. Minei,Paul E. Bankey,Jeffrey L. Johnson,Jason L. Sperry,Avery B. Nathens,Timothy R. Billiar,Michael West,Bernard H. Brownstein,Philip H. Mason,Henry V. Baker,Celeste C. Finnerty,Marc G. Jeschke,M. Cecilia Lopez,Matthew B. Klein,Richard L. Gamelli,Nicole S. Gibran,Brett D. Arnoldo,Weihong Xu,Yuping Zhang,Steven E. Calvano,Grace P. McDonald-Smith,David A. Schoenfeld,John D. Storey,J. Perren Cobb,H. Shaw Warren,Lyle L. Moldawer,David N. Herndon,Stephen F. Lowry,Ronald V. Maier,Ronald W. Davis,Ronald G. Tompkins,W. Xiao,M. Mindrinos,J. Seok,J. Cuschieri,R. Tompkins,Roger J. Davis,R. Maier,L. Moldawer,L. Hennessy,E. Moore,J. Minei,P. Bankey,J. Johnson,J. Sperry,A. Nathens,T. Billiar,M. West,B. Brownstein,D. Herndon,H. Baker,C. Finnerty,M. Jeschke,M. Lopez,M. Klein,R. Gamelli,N. Gibran,B. Arnoldo,G. McDonald-Smith,D. Schoenfeld,J. P. Cobb,Shaw Warren,A. Cuenca,S. Lowry,S. Calvano,Doug Hayden,P. Mason,H. Gao,J. Storey,Lily L. Altstein,Ulysses J. Balis,David G. Camp,K. De Asit,Brian G. Harbrecht,Shari Honari,Bruce A. McKinley,Carol L. Miller-Graziano,Frederick A. Moore,Grant E. O'Keefe,Laurence G. Rahme,Daniel G. Remick,Michael B. Shapiro,Richard D. Smith,Robert Tibshirani,Mehmet Toner,Bram Wispelwey,Wing Hung Wong +96 more
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TLDR
It is shown that critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes that alter the status of these genes in the immune system.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.read more
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Genomic responses in mouse models poorly mimic human inflammatory diseases
Seok Junhee Seok,Shaw Warren,G. Cuenca Alex,N. Mindrinos Michael,V. Baker Henry,Weihong Xu,Daniel R. Richards,Grace P. McDonald-Smith,Hong Gao,Laura Hennessy,Celeste C. Finnerty,Cecilia M Lopez,Shari Honari,Ernest E. Moore,Joseph P. Minei,Joseph Cuschieri,Paul E. Bankey,Jeffrey L. Johnson,Jason L. Sperry,Avery B. Nathens,Timothy R. Billiar,Michael West,Marc G. Jeschke,Matthew B. Klein,Richard L. Gamelli,Nicole S. Gibran,Bernard H. Brownstein,Carol L. Miller-Graziano,Steve E. Calvano,Philip H. Mason,J. Perren Cobb,Laurence G. Rahme,Stephen F. Lowry,Ronald V. Maier,Lyle L. Moldawer,David N. Herndon,Ronald W. Davis,Wenzhong Xiao,Wenzhong Xiao,Ronald G. Tompkins +39 more
TL;DR: This study shows that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another.
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A network-based analysis of systemic inflammation in humans
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