Immunological alterations in the endothelial barrier: a new predictive and therapeutic paradigm for sepsis

ABSTRACT

Introduction

Despite the fact incidence and mortality vary widely among regions, sepsis remains a major cause of morbidity and cost worldwide. The importance of the endothelial barrier in sepsis and infectious diseases is increasingly recognized; however, the underlying pathophysiology of the endothelial barrier in sepsis remains poorly understood.

Areas covered

Here we review the advances in basic and clinical research for relevant papers in PubMed database. We attempt to provide an updated overview of immunological alterations in endothelial dysfunction, discussing the central role of endothelial barrier involved in sepsis to provide new predictive and therapeutic paradigm for sepsis.

Expert opinion

Given its physiological and immunological functions in infectious diseases, the endothelial barrier has been dramatically altered in sepsis, suggesting that endothelial dysfunction may play a critical role in the pathogenesis of sepsis. Although many reliable biomarkers have been investigated to monitor endothelial activation and injury in an attempt to find diagnostic and therapeutic tools, there are no specific therapies to treat sepsis due to its complex pathophysiology. Since sepsis is initiated by both hyperinflammation and immunoparalysis occurring simultaneously, a ‘one-treatment-fits-all’ strategy for sepsis-induced immune injury and immunoparalysis is bound to fail, and an individualized ‘precision medicine’ approach is required.

KEYWORDS:

• Sepsis
• endothelial barrier
• pathogen infection
• biomarkers
• immunoparalysis

Article highlights

• Sepsis is a severe endothelial dysfunction syndrome caused by a dysregulated host response to microbial infection.

• Endothelial dysfunction may play a central role in the pathogenesis of sepsis.

• Many reliable biomarkers have been explored to monitor endothelial cell activation and dysfunction.

• Sepsis is initiated by both hyperinflammation and immunoparalysis occurring simultaneously.

• Immunotherapies with immunomodulatory activity highlight their implications for developing effective strategies to treat patients with sepsis.

• Restoring the endothelial barrier to physiological function represents a new area in the treatment of sepsis.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Natural Science Foundation of Hubei Province under Grant [2022CFB148].