title: Cumulative effects of bone and soft tissue injury on systemic inflammation: a pilot study.
abstract: BACKGROUND
  In multiply injured patients, bilateral femur fractures invoke a substantial systemic inflammatory impact and remote organ dysfunction. However, it is unclear whether isolated bone or soft tissue injury contributes to the systemic inflammatory response and organ injury after fracture.
  
  
  OBJECTIVE
  We therefore asked whether the systemic inflammatory response and remote organ dysfunction are attributable to the bone fragment injection, adjacent soft tissue injury, or both.
  
  
  METHODS
  Male C57/BL6 mice (8-10 weeks old, 20-30 g) were assigned to four groups: bone fragment injection (BF, n = 9) group; soft tissue injury (STI, n = 9) group; BF + STI (n = 9) group, in which both insults were applied; and control group, in which neither insult was applied. Animals were sacrificed at 6 hours. As surrogates for systemic inflammation, we measured serum IL-6, IL-10, osteopontin, and alanine aminotransferase (ALT) and nuclear factor (NF)-κB and myeloperoxidase (MPO) in the lung.
  
  
  RESULTS
  The systemic inflammatory response (mean IL-6 level) was similar in the BF (61.8 pg/mL) and STI (67.9 pg/mL) groups. The combination (BF + STI) of both traumatic insults induced an increase in mean levels of inflammatory parameters (IL-6: 189.1 pg/mL) but not in MPO levels (1.21 ng/mL) as compared with the BF (0.82 ng/mL) and STI (1.26 ng/mL) groups. The model produced little evidence of remote organ inflammation.
  
  
  CONCLUSIONS
  Our findings suggest both bone and soft tissue injury are required to induce systemic changes. The absence of remote organ inflammation suggests further fracture-associated factors, such as hemorrhage and fat liberation, may be more critical for induction of remote organ damage.
  
  
  CONCLUSIONS
  Both bone and soft tissue injuries contribute to the systemic inflammatory response.
authors.affiliation: Department of Orthopaedic Surgery, University of Aachen Medical Center, Pauwelsstr 30, 52074, Aachen, Germany. rpfeifer@ukaachen.de
authors.forename: Roman
authors.initials: R
authors.lastname: Pfeifer
authors.forename: Sophie
authors.initials: S
authors.lastname: Darwiche
authors.forename: Lauryn
authors.initials: L
authors.lastname: Kohut
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Pape
mesh_terms: D000818:Animals; D050723:Fractures, Bone / Q000097:blood / Q000378:metabolism*; D007249:Inflammation / Q000097:blood / Q000378:metabolism*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D053495:Osteopontin / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D010865:Pilot Projects; D017695:Soft Tissue Injuries / Q000097:blood / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D053495:Osteopontin; D016753:Interleukin-10; D009195:Peroxidase