The inflammatory response of endothelial cells – the cells that line blood vessels – contributes to the pathology of sepsis, a whole-body inflammatory response to infection. It has not been possible to modulate endothelial cell-induced inflammation as a strategy for treating sepsis.
Ryan Stark, M.D., and colleagues explored the possibility of inducing immune “tolerance” in endothelial cells. They pre-treated human endothelial cells with MPLA, a clinically used vaccine adjuvant that enhances the immune response. The investigators found that endothelial cells pre-treated with MPLA had reduced production of inflammatory factors after a subsequent challenge with bacterial toxin. They also characterized the signaling proteins involved in this induction of tolerance in the endothelial cells.
The findings, reported in the journal Clinical Science, show that compounds such as MPLA can induce “immune reprogramming” in endothelial cells. This reprogramming could be used therapeutically to blunt the inflammatory responses of endothelial cells to bacterial infection and prevent the negative consequences of sepsis.
This work was supported by grants from the National Institutes of Health (GM117367, GM104306).
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