Sepsis-associated encephalopathy: a vicious cycle of immunosuppression

Chao Ren,Ren-Qi Yao,Yong-Wen Feng,Hui Zhang,Yong-Ming Yao

doi:10.1186/s12974-020-1701-3

Abstract

Sepsis-associated encephalopathy (SAE) is commonly complicated by septic conditions, and is responsible for increased mortality and poor outcomes in septic patients. Uncontrolled neuroinflammation and ischemic injury are major contributors to brain dysfunction, which arises from intractable immune malfunction and the collapse of neuroendocrine immune networks, such as the cholinergic anti-inflammatory pathway, hypothalamic-pituitary-adrenal axis, and sympathetic nervous system. Dysfunction in these neuromodulatory mechanisms compromised by SAE jeopardizes systemic immune responses, including those of neutrophils, macrophages/monocytes, dendritic cells, and T lymphocytes, which ultimately results in a vicious cycle between brain injury and a progressively aberrant immune response. Deep insight into the crosstalk between SAE and peripheral immunity is of great importance in extending the knowledge of the pathogenesis and development of sepsis-induced immunosuppression, as well as in exploring its effective remedies.

Highlights

Sepsis is one of the major threats to the survival and prognosis of patients in intensive care units (ICUs) but lacks specific and effective treatments
The role of the immune response in the pathogenesis of sepsis associated encephalopathy Multiple factors are reportedly involved in the pathogenesis of sepsis-associated encephalopathy (SAE) (Fig. 1), including inflammatory cytokines, collapse of the blood–brain barrier (BBB), ischemic processes, alterations in neurotransmitters, and mitochondrial dysfunction, while the specific mechanism has not yet been established
Functional integrity and activity of Dendritic cell (DC) are closely related to the survival and prognosis of septic patients, while dysfunction of DCs has been identified as one of the major contributors to sepsis-induced immunosuppression and accounts for increased mortality and poor outcomes [77, 78]

Summary

Introduction

Sepsis is one of the major threats to the survival and prognosis of patients in intensive care units (ICUs) but lacks specific and effective treatments. The role of the immune response in the pathogenesis of sepsis associated encephalopathy Multiple factors are reportedly involved in the pathogenesis of SAE (Fig. 1), including inflammatory cytokines, collapse of the BBB, ischemic processes, alterations in neurotransmitters, and mitochondrial dysfunction, while the specific mechanism has not yet been established.

Results

Conclusion