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Lymphocyte modulation with FTY720 improves hemorrhagic shock survival in swine
Jason S Hawksworth1, J Christopher Graybill, Trevor S Brown
1Regenerative Medicine Department, Operational and Undersea Medicine Directorate, Naval Medical Research Center, Silver Spring, Maryland, United States of America.
Plos One
|May 5, 2012
Summary
Lymphocyte sequestration using FTY720 improved survival in a swine model of hemorrhagic shock and liver injury. This immunomodulation strategy reduced neutrophil infiltration and immune gene expression, suggesting potential for trauma patients.
Area of Science:
- Immunology
- Trauma Surgery
- Pharmacology
Background:
- Severe traumatic injury triggers inflammatory responses, leading to significant morbidity and mortality.
- Lymphocytes are key mediators in the early innate immune response to ischemia-reperfusion injury.
- Modulating lymphocyte activity post-hemorrhagic shock may mitigate secondary immunologic injury in trauma and surgical patients.
Purpose of the Study:
- To evaluate FTY720, a lymphocyte sequestration agent, as an immunomodulator in an experimental swine model of hemorrhagic shock with liver injury.
- To assess the impact of FTY720 on survival, immune cell distribution, and inflammatory markers.
Main Methods:
- Yorkshire swine with induced grade III liver injury and hemorrhagic shock were treated with FTY720 or a vehicle control.
- Survival was monitored over 3 days, with measurements of circulating leukocytes, neutrophils, and immunohistochemistry for CD3+ lymphocytes and myeloperoxidase (MPO).
- Liver immune-related gene expression was quantified using RT-PCR.
Main Results:
- FTY720 treatment significantly improved reperfusion survival (75% vs. 25%, p=0.047) and showed a trend towards improved overall survival (66.7% vs. 22.2%, p=0.081).
- FTY720 increased CD3+ lymphocytes in lymph nodes and spleen, indicating central sequestration, and decreased circulating and lung-infiltrating neutrophils.
- A reduction in liver immune-related gene expression was observed in the FTY720 group, with no infectious complications.
Conclusions:
- Lymphocyte sequestration with FTY720 enhances survival in experimental hemorrhagic shock with liver injury.
- This approach effectively reduces neutrophil-driven inflammation and immune dysregulation.
- FTY720 represents a promising immunomodulatory strategy to mitigate secondary immune injury following hemorrhagic shock.
