Dehydroepiandrosterone modulates the inflammatory response in a bilateral femoral shaft fracture model

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 TNF alpha, IL-1 beta, IL-6, IL-10, MCP-1, and KC concentrations were measured by Bio-Plex Pro (TM) 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-1 beta (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. Conclusion: We conclude that DHEA may be a treatment option to reduce systemic inflammation following musculoskeletal injuries although the pulmonary inflammatory reaction was not affected.