title: Distinct roles of trauma and transfusion in induction of immune modulation after injury.
abstract: BACKGROUND
  Trauma and transfusion can both alter immunity, and while transfusions are common among traumatically injured patients, few studies have examined their combined effects on immunity.
  
  
  METHODS
  We tracked the plasma levels of 41 immunomodulatory proteins in 56 trauma patients from time of injury up to 1 year later. In addition, a murine model was developed to distinguish between the effects of transfusion and underlying injury and blood loss.
  
  
  RESULTS
  Thirty-one of the proteins had a significant change over time after traumatic injury, with a mixed early response that was predominantly anti-inflammatory followed by a later increase in proteins involved in wound healing and homeostasis. Results from the murine model revealed similar cytokine responses to humans. In mice, trauma and hemorrhage caused early perturbations in a number of the pro- and anti-inflammatory mediators measured, and transfusion blunted early elevations in interleukin (IL)-6, IL-10, matrix metalloproteinase-9, and interferon-γ. Transfusion caused or exacerbated changes in monocyte chemotactic protein-1, IL-1α, IL-5, IL-15, and soluble E-selectin. Finally, trauma and hemorrhage alone increased CXCL1 and IL-13.
  
  
  CONCLUSIONS
  This work provides a detailed characterization of the major shift in the immunologic environment in response to trauma and transfusion and clarifies which immune mediators are affected by trauma and hemorrhage and which by transfusion.
authors.affiliation: Blood Systems Research Institute, San Francisco, California 94118, USA. rjackman@bloodsystems.org
authors.forename: Rachael P
authors.initials: RP
authors.lastname: Jackman
authors.forename: Garth H
authors.initials: GH
authors.lastname: Utter
authors.forename: Marcus O
authors.initials: MO
authors.lastname: Muench
authors.forename: John W
authors.initials: JW
authors.lastname: Heitman
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Munz
authors.forename: Robert W
authors.initials: RW
authors.lastname: Jackman
authors.forename: Hope H
authors.initials: HH
authors.lastname: Biswas
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Rivers
authors.forename: Leslie H
authors.initials: LH
authors.lastname: Tobler
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
mesh_terms: D000208:Acute Disease; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001803:Blood Transfusion; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000276:immunology / Q000628:therapy; D006801:Humans; D007107:Immune System / Q000276:immunology*; D056747:Immunomodulation / Q000276:immunology*; D007378:Interleukins / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018448:Models, Immunological; D013312:Stress, Physiological / Q000276:immunology; D014947:Wounds and Injuries / Q000276:immunology* / Q000628:therapy*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007378:Interleukins