Neutrophil activity in sepsis: a systematic review.

C.B Resende,V Nobre,I Borges,B.M Rezende,W.A Gonçalves,V Pinho,R Carneiro,M.M Teixeira

doi:10.1590/1414-431x20207851

Abstract

The neutrophil is an important cell in host defense against infections, acting as the first line of microorganism control. However, this cell exhibits dysregulated activity in sepsis and may contribute to the pathogenesis of the disease. This systematic review aimed to highlight the major scientific findings regarding neutrophil activity in sepsis reported in clinical and experimental research published in the last 10 years. The search was conducted in the Virtual Health Library of PAHO-WHO (BVS) and PubMed databases, and articles published between January 2007 and May 2017 in Portuguese, English, and Spanish were eligible. Article selection was carried out independently by two reviewers (CB and IB). A total of 233 articles were found, of which 87 were identified on PubMed and 146 on BVS. Eighty-two articles were duplicates. Of the remaining 151 articles, 19 met the inclusion criteria after title, abstract, and full-text analysis. Overall, research in clinical samples and animal models of sepsis showed reduced capacity of neutrophils to migrate and delayed apoptosis, but there was no consensus on the phagocytic activity of neutrophils in sepsis. Molecules, such as pentraxin 3 (PTX3), have been analyzed as potential diagnostic markers in sepsis but the diversity of soluble molecules detected in blood samples of sepsis patients did not enable further understanding of the correlation of these circulating molecules with neutrophil activity during sepsis. Optimal understanding of the function of neutrophils in sepsis remains a challenge that, if overcome, would eventually allow targeted therapeutic interventions in patients affected by this severe syndrome.

Highlights

Sepsis is defined as a dysregulated host response to an infectious agent, with dysfunction of one or more organ systems
Neutrophils are the first cells to migrate through the vascular epithelium and reach the site of infection [4]
Study selection was carried out by two independent reviewers (CB and IB) after discussion and agreement of the following eligibility criteria: original articles; neutrophil function clearly identified by name, function, or any direct mention regarding the analysis of this cell; a clear mention of direct neutrophil activity in the context of clinical or laboratory sepsis in the abstract; and studies with descriptions of neutrophil activity in clinical or laboratory sepsis

Summary

Introduction

Sepsis is defined as a dysregulated host response to an infectious agent, with dysfunction of one or more organ systems. Sepsis is a cascade of events originating from innate and adaptive immune responses; it is characterized by the activation of various cell types and release of both proinflammatory and anti-inflammatory molecules. In the initial phase of sepsis, a predominantly hyperinflammatory state caused by cellular interactions with the infectious agent develops, followed by a state of immune hyporesponsivity [2,3]. Neutrophils are the first cells to migrate through the vascular epithelium and reach the site of infection [4]. The chemokines CXCL1, CXCL2, leukotriene B4, and interleukin-8 (CXCL8) released during this stage act on leukocyte rolling by inducing stable binding between adhesion molecules and generating a concentration gradient that stimulates the transmigration of neutrophils from the bloodstream to the site of infection [5]

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Results

Conclusion