title: A genomic storm in critically injured humans.
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.
authors: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors: Wenzhong
authors: W
authors: Xiao
authors: Michael N
authors: MN
authors: Mindrinos
authors: Junhee
authors: J
authors: Seok
authors: Joseph
authors: J
authors: Cuschieri
authors: Alex G
authors: AG
authors: Cuenca
authors: Hong
authors: H
authors: Gao
authors: Douglas L
authors: DL
authors: Hayden
authors: Laura
authors: L
authors: Hennessy
authors: Ernest E
authors: EE
authors: Moore
authors: Joseph P
authors: JP
authors: Minei
authors: Paul E
authors: PE
authors: Bankey
authors: Jeffrey L
authors: JL
authors: Johnson
authors: Jason
authors: J
authors: Sperry
authors: Avery B
authors: AB
authors: Nathens
authors: Timothy R
authors: TR
authors: Billiar
authors: Michael A
authors: MA
authors: West
authors: Bernard H
authors: BH
authors: Brownstein
authors: Philip H
authors: PH
authors: Mason
authors: Henry V
authors: HV
authors: Baker
authors: Celeste C
authors: CC
authors: Finnerty
authors: Marc G
authors: MG
authors: Jeschke
authors: M Cecilia
authors: MC
authors: López
authors: Matthew B
authors: MB
authors: Klein
authors: Richard L
authors: RL
authors: Gamelli
authors: Nicole S
authors: NS
authors: Gibran
authors: Brett
authors: B
authors: Arnoldo
authors: Weihong
authors: W
authors: Xu
authors: Yuping
authors: Y
authors: Zhang
authors: Steven E
authors: SE
authors: Calvano
authors: Grace P
authors: GP
authors: McDonald-Smith
authors: David A
authors: DA
authors: Schoenfeld
authors: John D
authors: JD
authors: Storey
authors: J Perren
authors: JP
authors: Cobb
authors: H Shaw
authors: HS
authors: Warren
authors: Lyle L
authors: LL
authors: Moldawer
authors: David N
authors: DN
authors: Herndon
authors: Stephen F
authors: SF
authors: Lowry
authors: Ronald V
authors: RV
authors: Maier
authors: Ronald W
authors: RW
authors: Davis
authors: Ronald G
authors: RG
authors: Tompkins
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D002056:Burns / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016638:Critical Illness; D004731:Endotoxins / Q000008:administration & dosage; D005260:Female; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D014158:Transcription, Genetic; D015599:Trauma Severity Indices
chemical_list: D004731:Endotoxins