title: Role of the RAGE Axis during the Immune Response after Severe Trauma: A Prospective Pilot Study.
abstract: BACKGROUND
  Severe traumatization induces a complex pathophysiology, driven by the patient's own immune system. The initial activation is a result of damage-associated molecular patterns, which are released from disrupted and dying cells and recognized by immune receptors, for example, RAGE. In this study we aimed to evaluate the contribution of the RAGE axis to early and late immune responses.
  
  
  METHODS
  We enrolled 16 patients with severe trauma together with 10 patients after major abdominal surgery and 10 healthy volunteers. Blood samples were taken on admission and every 48 h for a total of 8 days. Plasma concentrations of various RAGE ligands as well as RAGE isoforms and IL-6 were measured by ELISA. Monocyte surface expression of RAGE and HLA-DR was assessed by flow cytometry.
  
  
  RESULTS
  High and transient levels of IL-6 and methylglyoxal characterize the early immune response after trauma, whereas samples from later time points provide evidence for a secondary release of RAGE ligands.
  
  
  CONCLUSIONS
  Our results provide evidence for a persisting activation of the RAGE axis while classical mediators like IL-6 disappear early. Considering the immunocompromised phenotype of the monocytes, the RAGE ligands might be substantial contributors to the well-known secondary stage of impaired immune responsiveness in trauma patients.
authors.affiliation: Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
authors.forename: Florian
authors.identifier: 0000-0001-8876-7430
authors.initials: F
authors.lastname: Uhle
authors.affiliation: Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Lichtenstern
authors.affiliation: Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
authors.forename: Thorsten
authors.identifier: 0000-0002-4570-877X
authors.initials: T
authors.lastname: Brenner
authors.affiliation: Department of Medicine I and Clinical Chemistry, Heidelberg University Hospital, 69120 Heidelberg, Germany.
authors.forename: Thomas
authors.identifier: 0000-0002-3232-4515
authors.initials: T
authors.lastname: Fleming
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Justus-Liebig-University, 35392 Giessen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Koch
authors.affiliation: Department of General and Thoracic Surgery, Justus-Liebig-University, 35392 Giessen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hecker
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital of Giessen-Marburg GmbH, Campus Giessen, 35392 Giessen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.affiliation: Department of Medicine I and Clinical Chemistry, Heidelberg University Hospital, 69120 Heidelberg, Germany.
authors.forename: Peter Paul
authors.initials: PP
authors.lastname: Nawroth
authors.affiliation: Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
authors.forename: Stefan
authors.identifier: 0000-0002-5541-8901
authors.initials: S
authors.lastname: Hofer
authors.affiliation: Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
authors.forename: Markus Alexander
authors.initials: MA
authors.lastname: Weigand
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Justus-Liebig-University, 35392 Giessen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Weismüller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood; D006801:Humans; D007108:Immune Tolerance; D015850:Interleukin-6 / Q000097:blood; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D010865:Pilot Projects; D011446:Prospective Studies; D011765:Pyruvaldehyde / Q000097:blood; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood / Q000276:immunology*; D013312:Stress, Physiological; D014947:Wounds and Injuries / Q000097:blood / Q000276:immunology*; D055815:Young Adult
chemical_list: C000593871:AGER protein, human; D006684:HLA-DR Antigens; C508600:IL6 protein, human; D015850:Interleukin-6; D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D011765:Pyruvaldehyde