Abstract

Sepsis and septic shock are among the leading causes of death in intensive care units worldwide. Numerous studies on their pathophysiology have revealed an imbalance in the inflammatory network leading to tissue damage, organ failure, and ultimately, death. Cytokines are important pleiotropic regulators of the immune response, which have a crucial role in the complex pathophysiology underlying sepsis. They have both pro- and anti-inflammatory functions and are capable of coordinating effective defense mechanisms against invading pathogens. On the other hand, cytokines may dysregulate the immune response and promote tissue-damaging inflammation. In this review, we address the current knowledge of the actions of pro- and anti-inflammatory cytokines in sepsis pathophysiology as well as how these cytokines and other important immunomodulating agents may be therapeutically targeted to improve the clinical outcome of sepsis.

Highlights

  • Sepsis, or the invasion of microbial pathogens into the bloodstream, is characterized by a systemic proinflammatory response, which can lead to severe sepsis and septic shock [1]

  • We address the current knowledge of the actions of pro- and anti-inflammatory cytokines in sepsis pathophysiology as well as how these cytokines and other important immunomodulating agents may be therapeutically targeted to improve the clinical outcome of sepsis

  • The administration of recombinant IL-10 protein to WT or IL-10 deficient mice increased survival and lengthened the therapeutic window for the rescue surgery. These results suggest that IL-10 might regulate the transition from early reversible sepsis to late irreversible septic shock

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Summary

Introduction

The invasion of microbial pathogens into the bloodstream, is characterized by a systemic proinflammatory response, which can lead to severe sepsis and septic shock [1]. Severe sepsis, and septic shock are major healthcare problems worldwide; they affect millions of people each year, and their incidence increases annually [2, 3]. Despite significant advances in intensive care treatment over the last years, septic shock remains associated with high mortality rates [4]. An epidemiologic study reported that septic shock is the most common cause of death in noncoronary intensive care units, and the tenth leading cause of death overall in highincome countries [2]. Reasons for the anticipated increase in sepsis incidence and its associated mortality include the increasing number of immunocompromised patients, emerging antibiotic resistance in microorganisms, and the aging population [6]. Sepsis was identified as one of the five conditions that account for the most expensive hospital stays in the United States [7]

Definition of Sepsis
Pathophysiology of Sepsis
Initiation of the Immune Response
Cytokines in Sepsis Pathophysiology
Proinflammatory Cytokines
Anti-Inflammatory Cytokines
Immunomodulating Treatment Strategies for Sepsis
Findings
Conclusion
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