Thalidomide prolongs survival after experimental musculoskeletal injury, through an effect on mononuclear apoptosis

详细信息    查看全文

• 作者：Konstantinos Panousis ; MD ; PhD^a ; Vassilios S. Nikolaou ; MD ; PhD ; MSc^a ; ^{vassilios.nikolaou@gmail.com" class="auth_mail} ; Thomas Tsaganos ; MD ; PhD^b ; Stergios Lallos ; MD^a ; Evangelos J. Giamarellos-Bourboulis ; MD ; PhD^b ; Nicolas Efstathopoulos ; MD ; PhD^a
• 关键词：Lymphocytes ; TNF ; Systemic inflammation ; Trauma ; Immunomodulation
• 刊名：Journal of Surgical Research
• 出版年：1 May, 2014
• 年：2014
• 卷：188
• 期：1
• 页码：198-205
• 全文大小：910 K

文摘

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-伪), survival of animals that received thalidomide would be significantly prolonged.

Material and 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聽h. Survival was recorded and bacterial growth in blood and organs was measured after animal death or sacrifice. Blood was sampled for TNF-伪 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-伪 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-伪 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.