What's New in Shock, December 2017?

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This issue of SHOCK is both intriguing and exciting with many new reports probing fundamental gaps in knowledge at the epicenter of chronic inflammation, immune dysregulation, sepsis pathophysiology, traumatic injury, and persistent catabolism. It is a pleasure and privilege to read, deconstruct, and assimilate the scientific reports in this issue against the greater stage of human knowledge. The opportunity to experience firsthand the insight, passion, and at times frustration that each of these reports has added to our field is priceless. More importantly, many of the studies in this issue have been generated outside the confines of the Unites States, indicating that the Journal readership, desirability, and notoriety are expanding and scientifically valuable.
Immune modulatory therapies aimed at bolstering desirable cellular functions such as bacterial eradication and wound healing, while mitigating undesirable aspects of ongoing inflammation that promulgate organ injury, are of growing interest. Endo et al. sought to explore the functional change in neutrophils in patients diagnosed with severe sepsis or septic shock before therapeutic intervention (1). The authors first demonstrate that neutrophil priming state was significantly elevated at presentation, further elevated on day 3, and subsequently returned to initial levels by day 7 in the face of inflammation resolution. Furthermore, the authors show that neutrophil transmigration and adhesion were suppressed most strongly on day 0, and gradually recovered over the next 7 days, by measuring CXC chemokine receptor 2 and paired immunoglobulin-like receptor α expression. To conclude their studies, the researchers show that contrary to patient clinical trajectory, neutrophil priming state was most robust 3 days after sepsis diagnosis. Considering these insights juxtaposed against the recent upsurge in interest for applications of immune modulatory therapies to improve the recovery phase of sepsis, these findings provide an important timeline for the initiation of potential agents aimed at neutrophil cellular modulation.
Moving from pure innate immunity onto the interaction between the innate and adaptive immune systems and their role in sepsis, Albertsmeier et al. sought to determine which immune cell initiates postoperative immunosuppression during sepsis (2). The researchers isolated T lymphocytes and monocytes from abdominal surgery patients preoperatively as well as in those patients who developed sepsis. The results showed a postoperative suppression of CD3+ cells as well as the activation marker CD28 on lymphocytes. Furthermore, there was a significant increase in CD14+ and CD14+CD86+, and CD14+HLA-DR+ monocyte populations postoperatively. Not surprisingly, in sepsis patients, monocyte HLA-DR expression was reduced compared with postoperative patient levels. In response to these findings the authors performed a complex series of coculture experiments using T-cells and monocytes from postoperative and naïve patients aimed at determining which cell type mediates the immune suppressive properties in sepsis. The collective results from these studies led the researchers to conclude that T-cells are suppressed postoperatively but still able to trigger monocyte cytokine release. However, on the contrary, activated monocytes seem to facilitate T-cell suppression. These findings not only shed much needed light on the subject of sepsis induced immune suppression, but also the fact that surgery itself can induce immune suppressive cellular properties that may prove to be detrimental to effective wound healing and speedy recovery.
Dovetailing from sepsis induced innate and adaptive immune dysregulation. Masao Kaneki single handedly tackles the daunting task of detailing the topic of metabolic inflammatory complexes in sepsis and why septic cachexia may very well be placed on the ever growing list of potential therapeutic targets to improve sepsis survival (3). The author eloquently explains how metabolic alterations associated with the host inflammatory response, such as mitochondrial dysfunction and metabolic shift, are closely linked through a complex signaling array of interdigitating molecules and compounds.
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