The online version of this article (doi:10.1186/1476-9255-9-34) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
Conceived and designed the experiments: EE DT. Performed the experiments: JSH JCG SG TB. Analyzed the data: JSH JCG TB SW TD EE JSH SG. Wrote the paper: JSH JCG. Supervised the protocol that obtained the information that lead to the writing of the manuscript: TB TD DT EE. Final revisions of the manuscript: DT TB TD EE. All authors read and approved the final manuscript
Hemorrhagic shock results in systemic activation of the immune system and leads to ischemia-reperfusion injury. Lymphocytes have been identified as critical mediators of the early innate immune response to ischemia-reperfusion injury, and immunomodulation of lymphocytes may prevent secondary immunologic injury in surgical and trauma patients.
Yorkshire swine were anesthetized and underwent a grade III liver injury with uncontrolled hemorrhage to induce hemorrhagic shock. Experimental groups were treated with a lymphocyte depletional agent, porcine polyclonal anti-thymocyte globulin (PATG) (n = 8) and compared to a vehicle control group (n = 9). Animals were observed over a 3 day survival period. Circulating lymphocytes were examined with FACS analysis for CD3/CD4/CD8, and central lymphocytes with mesenteric lymph node and spleen staining for CD3. Circulating and lung tissue16 infiltrating neutrophils were measured. Circulating CD3 lymphocytes in the blood and in central lymphoid organs (spleen/lymph node) were stained and evaluated using FACS analysis. Immune-related gene expression from liver tissue was quantified using RT-PCR.
The overall survival was 22% (2/9) in the control and 75% (6/8) in the PATG groups, p = 0.09; during the reperfusion period (following hemorrhage) survival was 25% (2/8) in the control and 100% (6/6) in the PATG groups, p = 0.008. Mean blood loss and hemodynamic profiles were not significantly different between the experimental and control groups. Circulating CD3+CD4+ lymphocytes were significantly depleted in the PATG group compared to control. Lymphocyte depletion in the setting of hemorrhagic shock also significantly decreased circulating and lung tissue infiltrating neutrophils, and decreased expression of liver ischemia gene expression.
Lymphocyte manipulation with a depletional (PATG) strategy improves reperfusion survival in experimental hemorrhagic shock using a porcine liver injury model. This proof of principle study paves the way for further development of immunomodulation approaches to ameliorate secondary immune injury following hemorrhagic shock.
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- Lymphocyte Depletion in Experimental Hemorrhagic Shock in Swine
Jason S Hawksworth
Trevor S Brown
Suzanne M Gillern
Shannon M Wallace
Thomas A Davis
Eric A Elster
Doug K Tadaki
- BioMed Central
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