title: Early down-regulation of the pro-inflammatory potential of monocytes is correlated to organ dysfunction in patients after severe multiple injury: a cohort study.
abstract: BACKGROUND
  Severe tissue trauma results in a general inflammatory immune response (SIRS) representing an overall inflammatory reaction of the immune system. However, there is little known about the functional alterations of monocytes in the early posttraumatic phase, characterized by the battle of the individual with the initial trauma.
  
  
  METHODS
  Thirteen patients with severe multiple injury; injury severity score (ISS) >16 points (17 to 57) were included. The cytokine synthesis profiles of monocytes were characterized on admission, and followed up 6, 12, 24, 48, and 72 hours after severe multiple injury using flow cytometry. Whole blood was challenged with lipopolysaccharide (LPS) and subsequently analyzed for intracellular monocyte-related TNF-alpha, IL-1beta, IL-6, and IL-8. The degree of organ dysfunction was assessed using the multiple organ dysfunction syndrome (MODS)-score of Marshall on admission, 24 hours and 72 hours after injury.
  
  
  RESULTS
  Our data clearly show that the capacity of circulating monocytes to produce these mediators de novo was significantly diminished very early reaching a nadir 24 hours after severe injury followed by a rapid and nearly complete recovery another 48 hours later compared with admission and controls, respectively. In contrast to the initial injury severity, there was a significant correlation detectable between the clinical signs of multiple organ dysfunction and the ex vivo cytokine response.
  
  
  CONCLUSIONS
  As our data derived from very narrow intervals of measurements, they might contribute to a more detailed understanding of the early immune alterations recognized after severe trauma. It can be concluded that indeed as previously postulated an immediate hyperactivation of circulating monocytes is rapidly followed by a substantial paralysis of cell function. Moreover, our findings clearly demonstrate that the restricted capacity of monocytes to produce proinflammatory cytokines after severe injury is not only an in vitro phenomenon but also undistinguishable associated with the onset of organ dysfunction in the clinical scenario.
authors.affiliation: Department of Orthopaedic Surgery and Traumatology, Klinikum Rechts der Isar, Technische Universitaet, 81675 Munich, Germany. chlodwig.kirchhoff@mac.com
authors.forename: Chlodwig
authors.initials: C
authors.lastname: Kirchhoff
authors.forename: Peter
authors.initials: P
authors.lastname: Biberthaler
authors.forename: Wolf E
authors.initials: WE
authors.lastname: Mutschler
authors.forename: Eugen
authors.initials: E
authors.lastname: Faist
authors.forename: Marianne
authors.initials: M
authors.lastname: Jochum
authors.forename: Siegfried
authors.initials: S
authors.lastname: Zedler
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D009000:Monocytes / Q000276:immunology*; D009102:Multiple Organ Failure / Q000276:immunology*; D009104:Multiple Trauma / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha