Potential Targets to Mitigate Trauma- or Sepsis-Induced Immune Suppression

Abstract

In sepsis and trauma, pathogens and injured tissue provoke a systemic inflammatory reaction which can lead to overwhelming inflammation. Concurrent with the innate hyperinflammatory response is adaptive immune suppression that can become chronic. A current key issue today is that patients who undergo intensive medical care after sepsis or trauma have a high mortality rate after being discharged. This high mortality is thought to be associated with persistent immunosuppression. Knowledge about the pathophysiology leading to this state remains fragmented. Immunosuppressive cytokines play an essential role in mediating and upholding immunosuppression in these patients. Specifically, the cytokines Interleukin-10 (IL-10), Transforming Growth Factor-β (TGF-β) and Thymic stromal lymphopoietin (TSLP) are reported to have potent immunosuppressive capacities. Here, we review their ability to suppress inflammation, their dynamics in sepsis and trauma and what drives the pathologic release of these cytokines. They do exert paradoxical effects under certain conditions, which makes it necessary to evaluate their functions in the context of dynamic changes post-sepsis and trauma. Several drugs modulating their functions are currently in clinical trials in the treatment of other pathologies. We provide an overview of the current literature on the effects of IL-10, TGF-β and TSLP in sepsis and trauma and suggest therapeutic approaches for their modulation.

Keywords: IL-10; chronic critical illness; immunosuppression; thymic stromal lymphopoietin; transforming growth factor β.