Profiling Cytokine Expression in Trauma Patients Before and After TLR Stimulation
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CitationLevers, Najah A. 2017. Profiling Cytokine Expression in Trauma Patients Before and After TLR Stimulation. Master's thesis, Harvard Medical School.
AbstractTrauma is the leading cause of morbidity and mortality worldwide for individuals under the age of 45. Despite advances in emergency care, infection continues to be a major complication contributing to significantly high death rates. This is prevalent because traumatic injuries induce a complex host response mediated by pattern recognition receptors that disrupt immune homeostasis and predispose trauma patients to opportunistic infections. Recent studies have demonstrated the immunotherapeutic benefits of using a TLR9 agonist, CpG-ODN in mouse models of trauma. Therefore, it is imperative to continue to investigate the biological effects of CpG-ODN as well as other TLR agonists in order to develop an approach that can protect injured people from infections, restore immune system homeostasis and reduce mortality rates among trauma patients.
We hypothesize that human immune cells will react to TLR9 stimulation to suggest translation capability of TLR9 agonist immunotherapy. In addition, we predict that an A-Class CpG-ODN will stimulate beneficial self-regulating immune stimulatory responses.
We looked at human peripheral blood immune cells. These cells were stimulated with either CpG-ODN 2336 or LPS. After stimulation, we used Luminex technology as a systems immunology research tool to identify specific cytokine responses to CpG-ODN 2336 and LPS activation.
We report that human immune cells have significant cytokine production when stimulated with CpG-ODN 2336 and LPS. Some of these signature cytokines include TNFα, IL-1α, IL-1α, IL-6, IL-10, MCP-1, IL-1Ra, MIP-1β, RANTES and GM-CSF. Stimulation with CpG-ODN 2336 produced a much less potent inflammatory response than LPS, suggesting its non-toxic properties. However, it still induced a sufficient response to potentially activate cells to fight infection.
These results indicate that signature cytokine concentrations are induced or sustained when human immune cells are activated with TLR9 agonists. In addition, TLR9 agonists have implications for fighting infection and restoring immune system homeostasis. Further research is necessary to understand the immunotherapeutic potential of using CpG-ODNs to improve outcomes for trauma and infection.
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