Characterization of Early Peripheral Immune Responses in Patients with Sepsis and Septic Shock.

Jesús Beltrán-García,Germán Casabó-Vallés,Eva García-López,Federico V Pallardó,José-Enrique O’Connor,Guadalupe Herrera,Rebeca Osca-Verdegal,Beatriz Jávega,José Luis García-Giménez,José Ferreres,María Rodriguez-Gimillo,Nieves Carbonell

doi:10.3390/biomedicines10030525

Abstract

(1) Background: Sepsis is a life-threatening condition caused by an abnormal host response to infection that produces altered physiological responses causing tissue damage and can result in organ dysfunction and, in some cases, death. Although sepsis is characterized by a malfunction of the immune system leading to an altered immune response and immunosuppression, the high complexity of the pathophysiology of sepsis requires further investigation to characterize the immune response in sepsis and septic shock. (2) Methods: This study analyzes the immune-related responses occurring during the early stages of sepsis by comparing the amounts of cytokines, immune modulators and other endothelial mediators of a control group and three types of severe patients: critically ill non-septic patients, septic and septic shock patients. (3) Results: We showed that in the early stages of sepsis the innate immune system attempts to counteract infection, probably via neutrophils. Conversely, the adaptive immune system is not yet fully activated, either in septic or in septic shock patients. In addition, immunosuppressive responses and pro-coagulation signals are active in patients with septic shock. (4) Conclusions: The highest levels of IL-6 and pyroptosis-related cytokines (IL-18 and IL-1α) were found in septic shock patients, which correlated with D-dimer. Moreover, endothelial function may be affected as shown by the overexpression of adhesion molecules such as s-ICAM1 and E-Selectin during septic shock.

Highlights

Sepsis is a life-threatening condition that occurs as a consequence of a dysregulated host response to infection, which can evolve to tissue damage and organ dysfunction and thereby increase the risk of death [1,2]
We looked for the white blood cell and platelet counts in the clinical records and observed that polymorphonuclear cells were increased in sepsis and septic shock patients when compared to critically ill non-septic patients
Our results indicate that pyroptosis is an important player in the orchestration of innate immune response at least in the first stages of infection, contributing to adverse phenotypes that occur during the pathophysiology of sepsis (Figure 8)

Summary

Introduction

Sepsis is a life-threatening condition that occurs as a consequence of a dysregulated host response to infection, which can evolve to tissue damage and organ dysfunction and thereby increase the risk of death (in-hospital mortality above 10%) [1,2]. Cells of the innate immune system release high levels of pro-inflammatory cytokines triggering a “cytokine storm” and sometimes induce apoptosis of immune cells during the first hours of sepsis, leading to early death in septic patients [5]. It is of note that the exacerbated hyperinflammatory response produced can cause damage in uninfected tissues and lead to the dysfunction of different organs and systems inducing hypotension, vasculature damage and clotting events, which contribute to the worsening of patients and death [8,9,10]

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