Immune Aspects of Sepsis and Hope for New Therapeutics
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Marked alterations of the innate and adaptive immune response follow invasive infection and generalized inflammatory states. If left unchecked, this state of immune dysregulation contributes to a myriad of maladaptive cellular responses that culminate in multiple organ dysfunction, septic shock, and lethality. The molecular details of the cell-signaling networks that underlie the pathophysiology of systemic inflammation and sepsis are now increasingly well understood. While a vigorous and effective immune response to invasive pathogens is essential for microbial clearance and host survival, nonresolving, generalized inflammation can induce diffuse endovascular damage, increased capillary permeability, coagulopathy, and widespread tissue damage. Current evidence indicates that a state of relative immune suppression often accompanies sepsis and might provide novel therapeutic options in some patients. An expanding number of potential therapeutic options are now in clinical development to reestablish control and promote resolution over sepsis-induced systemic inflammation and organ dysfunction.
KeywordsLipopolysaccharide Sepsis Septic shock Toll-like receptors Co-stimulatory immune signals Co-inhibitory immune signals Sepsis interventions Hemoperfusion Apheresis
Dr. S. Opal has served as a consultant for Medimmune, Biotest, and Arsanis, received grant support for his institution fromAstra-Zenaca, Agennix, Asahi Kasel, David Horn LLC, Baxter, and Sirtris, and has served on data- and safety-monitoring boards for Sangart, Spectral Diagnostics, and Atoxio. Dr. S. LaRosa has served as a consultant for Ex Thera Medical and Agennix AG.
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