title: Thalidomide prolongs survival after experimental musculoskeletal injury, through an effect on mononuclear apoptosis.
abstract: BACKGROUND
  This study was conducted to investigate the effects of intravenous thalidomide administration in an experimental model of musculoskeletal trauma. We hypothesized that because thalidomide inhibits secretion of tumor necrosis factor alpha (TNF-α), survival of animals that received thalidomide would be significantly prolonged.
  
  
  METHODS
  After an open fracture of the right femur, 24 rabbits were randomly assigned to control and thalidomide groups. Intravenous therapy with thalidomide was started 30 min after fracture. Hemodynamic monitoring of all animals was performed for 4 h. Survival was recorded and bacterial growth in blood and organs was measured after animal death or sacrifice. Blood was sampled for TNF-α measurement and for isolation of peripheral blood mononuclear cells (PBMCs). Apoptosis of PBMCs was measured by flow cytometry.
  
  
  RESULTS
  Survival was significantly prolonged in the thalidomide group. Apoptosis of PBMCs was increased in the control group compared with the thalidomide group at 24 h. There were no differences in vital signs, blood and tissue cultures, and serum TNF-α concentration between the two groups.
  
  
  CONCLUSIONS
  Intravenous thalidomide prolonged survival in an experimental model of severe musculoskeletal injury in rabbits. Its mechanism of action did not involve TNF-α suppression but prevention of mononuclear apoptosis. In view of these promising results, further research is needed to clarify the immunomodulatory mechanism of action of thalidomide and its potential use for the management of severe trauma.
authors.affiliation: 2nd Department of Orthopaedics, University of Athens, Medical School, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Panousis
authors.affiliation: 2nd Department of Orthopaedics, University of Athens, Medical School, Greece. Electronic address: vassilios.nikolaou@gmail.com.
authors.forename: Vassilios S
authors.initials: VS
authors.lastname: Nikolaou
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Greece.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tsaganos
authors.affiliation: 2nd Department of Orthopaedics, University of Athens, Medical School, Greece.
authors.forename: Stergios
authors.initials: S
authors.lastname: Lallos
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Greece.
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.affiliation: 2nd Department of Orthopaedics, University of Athens, Medical School, Greece.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Efstathopoulos
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D005264:Femoral Fractures / Q000150:complications*; D005597:Fractures, Open / Q000150:complications*; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000517:prevention & control*; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide
keywords: Immunomodulation; Lymphocytes; Systemic inflammation; TNF; Trauma