title: Plasma levels of danger-associated molecular patterns are associated with immune suppression in trauma patients.
abstract: OBJECTIVE
  Danger-associated molecular patterns (DAMPs) released of trauma could contribute to an immune suppressed state that renders patients vulnerable towards nosocomial infections. We investigated DAMP release in trauma patients, starting in the prehospital phase, and assessed its relationship with immune suppression and nosocomial infections.
  
  
  METHODS
  Blood was obtained from 166 adult trauma patients at the trauma scene, emergency room (ER), and serially afterwards. Circulating levels of DAMPs and cytokines were determined. Immune suppression was investigated by determination of HLA-DRA gene expression and ex vivo lipopolysaccharide-stimulated cytokine production.
  
  
  RESULTS
  Compared with healthy controls, plasma levels of nuclear DNA (nDNA) and heat shock protein-70 (HSP70) but not mitochondrial DNA were profoundly increased immediately following trauma and remained elevated for 10 days. Plasma cytokines were increased at the ER, and levels of anti-inflammatory IL-10 but not of pro-inflammatory cytokines peaked at this early time-point. HLA-DRA expression was attenuated directly after trauma and did not recover during the follow-up period. Plasma nDNA (r = -0.24, p = 0.006) and HSP70 (r = -0.38, p < 0.0001) levels correlated negatively with HLA-DRA expression. Ex vivo cytokine production revealed an anti-inflammatory phenotype already at the trauma scene which persisted in the following days, characterized by attenuated TNF-α and IL-6, and increased IL-10 production. Finally, higher concentrations of nDNA and a further decrease of HLA-DRA expression were associated with infections.
  
  
  CONCLUSIONS
  Plasma levels of DAMPs are associated with immune suppression, which is apparent within minutes/hours following trauma. Furthermore, aggravated immune suppression during the initial phase following trauma is associated with increased susceptibility towards infections.
authors.affiliation: Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Internal Mail 710, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.|Department of Anesthesiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Timmermans
authors.affiliation: Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Internal Mail 710, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.|Department of Anesthesiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Kox
authors.affiliation: Department of Anesthesiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.|Helicopter Emergency Medical Service, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Vaneker
authors.affiliation: Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Internal Mail 710, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Berg
authors.affiliation: Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Internal Mail 710, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.|Department of Anesthesiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Aaron
authors.initials: A
authors.lastname: John
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: van Laarhoven
authors.affiliation: Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Internal Mail 710, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: van der Hoeven
authors.affiliation: Department of Anesthesiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Scheffer
authors.affiliation: Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Internal Mail 710, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Peter.Pickkers@radboudumc.nl.
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
mesh_terms: D000328:Adult; D000368:Aged; D002467:Cell Nucleus; D003428:Cross Infection / Q000097:blood / Q000276:immunology; D016207:Cytokines / Q000097:blood; D004247:DNA / Q000097:blood; D004272:DNA, Mitochondrial / Q000097:blood; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000097:blood; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged; D014947:Wounds and Injuries / Q000097:blood* / Q000276:immunology*
chemical_list: D016207:Cytokines; D004272:DNA, Mitochondrial; D018840:HSP70 Heat-Shock Proteins; D004247:DNA
keywords: DAMPs; Immune suppression; Infection; Injury; Trauma