title: Dehydroepiandrosterone modulates the inflammatory response in a bilateral femoral shaft fracture model.
abstract: BACKGROUND
  Dehydroepiandrosterone (DHEA) has been shown to have immunomodulatory effects after hemorrhage and sepsis. The present study analyzes whether DHEA is also involved in the mediation of inflammatory stimuli induced by bilateral femoral shaft fracture.
  
  
  METHODS
  Male C57/BL6 mice (6 per group) were subjected to closed bilateral femoral shaft fracture with intramedullary nailing followed by administration of either 25 mg/kg/24 h DHEA diluted in saline with 0.1% ethanol or saline with 0.1% ethanol. The sham group was treated by isolated intramedullary nailing without fracture. Animals were sacrificed after 6, 24, or 72 h. Serum TNFα, IL-1β, IL-6, IL-10, MCP-1, and KC concentrations were measured by Bio-Plex ProTm analysis. Acute pulmonary inflammation was assessed by histology, pulmonary myeloperoxidase (MPO) activity, and pulmonary IL-6 concentration.
  
  
  RESULTS
  DHEA was associated with a decrease in the systemic inflammatory response induced by bilateral femoral fracture, especially systemic IL-6 (322.2 vs. 62.5 pg/mL; P = 0.01), IL-1β (1,422.6 vs. 754.1 pg/mL; P = 0.05), and MCP-1 (219.4 vs. 44.1 pg/mL; P >0.01) levels. No changes in pulmonary inflammation were measured.
  
  
  CONCLUSIONS
  We conclude that DHEA may be a treatment option to reduce systemic inflammation following musculoskeletal injuries although the pulmonary inflammatory reaction was not affected.
authors.affiliation: Department of Orthopaedic Trauma Surgery, Faculty of Medicine, RWTH Aachen University, Pauwelsstraβe 30, Aachen 52074, Germany. plichte@ukaachen.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Lichte
authors.forename: Roman
authors.initials: R
authors.lastname: Pfeifer
authors.forename: Britta Elisa
authors.initials: BE
authors.lastname: Werner
authors.forename: Petra
authors.initials: P
authors.lastname: Ewers
authors.forename: Mersedeh
authors.initials: M
authors.lastname: Tohidnezhad
authors.forename: Thomas
authors.initials: T
authors.lastname: Pufe
authors.forename: Frank
authors.initials: F
authors.lastname: Hildebrand
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Pape
authors.forename: Philipp
authors.initials: P
authors.lastname: Kobbe
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000097:blood; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000150:complications* / Q000601:surgery; D005594:Fracture Fixation, Intramedullary; D007249:Inflammation / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D003687:Dehydroepiandrosterone