Abstract
BackgroundDehydroepiandrosterone (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.MethodsMale 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.ResultsDHEA 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.ConclusionWe conclude that DHEA may be a treatment option to reduce systemic inflammation following musculoskeletal injuries although the pulmonary inflammatory reaction was not affected.
Highlights
Dehydroepiandrosterone (DHEA) has been shown to have immunomodulatory effects after hemorrhage and sepsis
These post-traumatic changes might result in a relevant impairment of lung function (for example, acute lung injury (ALI) or Adult Respiratory Distress Syndrome (ARDS)) which represents a frequent complication after long bone fractures in general, but after bilateral femoral shaft fractures [10]
Plasma cytokine response The systemic release of IL-6 was significantly elevated at 6 h after bilateral femoral shaft fracture compared to the sham group
Summary
Dehydroepiandrosterone (DHEA) has been shown to have immunomodulatory effects after hemorrhage and sepsis. Androstendion, a metabolite of DHEA, In previous studies from our group bilateral femoral fractures were associated with a systemic inflammatory response and a migration of inflammatory cells into the pulmonary tissue [7,8,9]. These post-traumatic changes might result in a relevant impairment of lung function (for example, acute lung injury (ALI) or Adult Respiratory Distress Syndrome (ARDS)) which represents a frequent complication after long bone fractures in general, but after bilateral femoral shaft fractures [10]. The control of systemic inflammation as well as the maintenance of pulmonary function seem to be essential goals in the treatment of musculoskeletal injuries
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