title: The role of fracture-associated soft tissue injury in the induction of systemic inflammation and remote organ dysfunction after bilateral femur fracture.
abstract: OBJECTIVE
  The storage of preformed cytokines in soft tissue as well as the immunocompetence of adipocytes has been reported. We hypothesized that fracture-associated soft tissue injury plays a pivotal role in the induction of systemic inflammation and remote organ dysfunction after fracture.
  
  
  METHODS
  Male C57/BL6 mice sustained either severe soft tissue injury to both thighs (STI), bilateral femur fracture with minimal soft tissue injury (Fx), or the combination of both (Fx+STI) and were euthanized 6 hours after injury. Serum cytokine concentrations were measured using the Luminex multiplexing platform, and serum ALT levels were measured with the Vitros 950 Chemistry System. Hepatic myeloperoxidase activity, a marker for polymorphonuclear cell infiltration, and hepatic IL-6 levels were determined using ELISA kits. Hepatic permeability changes were assessed via measurement of edema formation.
  
  
  RESULTS
  STI as well as Fx both induced significantly elevated serum IL-6 and L-10 levels as compared with Sham animals (P < 0.05). Further, serum IL-6 and IL-10 levels were significantly higher after STI as compared with Fx (P < 0.05). Serum KC and MCP-1 levels were significantly elevated after STI but not after Fx (P < 0.05). STI as well as Fx resulted in significantly increased serum ALT levels and hepatic polymorphonuclear cell infiltration. The combination of both injuries resulted in further increased systemic inflammatory mediators as well as marked liver inflammation and dysfunction represented by significantly elevated serum ALT levels, hepatic polymorphonuclear cell infiltration, hepatic IL-6 concentrations, and hepatic edema formation as compared with Sham animals (P < 0.05).
  
  
  CONCLUSIONS
  Although STI and Fx both induced a systemic inflammatory response, this was more pronounced after STI. However, the combination of both injuries (Fx+STI) was required to induce marked liver dysfunction. Our data indicate that fracture-associated soft tissue injury is a major contributor to the systemic inflammatory response after bilateral femur fracture. This should be recognized especially in multiply injured patients, who are susceptible to systemic inflammation with remote organ dysfunction.
authors.affiliation: Department of Orthopedic Surgery, University of Pittsburghm Kaufmann Medical Building, Pittsburgh, PA 15213, USA. kobbep@upmc.edu
authors.forename: Philipp
authors.initials: P
authors.lastname: Kobbe
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
authors.forename: David J
authors.initials: DJ
authors.lastname: Kaczorowski
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Pape
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004487:Edema / Q000201:enzymology / Q000473:pathology; D005264:Femoral Fractures / Q000097:blood / Q000150:complications / Q000276:immunology*; D006614:Hindlimb / Q000293:injuries; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000276:immunology*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D017695:Soft Tissue Injuries / Q000097:blood / Q000209:etiology / Q000276:immunology*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D015850:Interleukin-6; D016753:Interleukin-10; D009195:Peroxidase