Natural Killer Cell Assessment in Peripheral Circulation and Bronchoalveolar Lavage Fluid of Patients with Severe Sepsis: A Case Control Study.

Paulo Souza-Fonseca-Guimaraes,Lidiane Maria Boldrini Leite,Alexandra Cristina Senegaglia,Fernando Souza-Fonseca-Guimaraes,Anita Nishiyama,Caroline Natânia De Souza-Araujo,Fernando Guimaraes

doi:10.3390/ijms18030616

Abstract

Sepsis is a complex systemic inflammatory syndrome, the most common cause of which is attributed to systemic underlying bacterial infection. The complete mechanisms of the dynamic pro- and anti-inflammatory processes underlying the pathophysiology of sepsis remain poorly understood. Natural killer (NK) cells play a crucial role in the pathophysiology of sepsis, leading to exaggerated inflammation due their rapid response and production of pro-inflammatory cytokines such as interferon gamma (IFN-γ). Several studies have already shown that NK cells undergo lymphopenia in the peripheral blood of patients with sepsis. However, our understanding of the mechanisms behind its cellular trafficking and its role in disease development is restricted to studies in animal models. In this study, we aimed to compare the human NK cell subset (CD56bright or dim) levels in the peripheral blood and bronchoalveolar lavage (BAL) fluid of sepsis patients. We conducted a case-control study with a sample size consisting of 10 control patients and 23 sepsis patients enrolled at the Hospital Cajuru (Curitiba/PR, Brazil) from 2013 to 2015. Although we were able to confirm previous observations of peripheral blood lymphopenia, no significant differences were detected in NK cell levels in the BAL fluid of these patients. Overall, these findings strengthened the evidence that peripheral blood lymphopenia is likely to be associated with cell death as a consequence of sepsis.

Highlights

Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection [1,2].Currently, sepsis is the tenth leading cause of death in high-income countries, accounting for more than 210,000 annual deaths in the USA [3]
Twenty-three patients who were characterized as having severe sepsis had evidence of primary infection in the lungs, and displayed clinical criteria of sepsis (fever or hypothermia, tachycardia, tachypnea, leukocytosis (>12,000) or leukopenia (10%)), or an increased sequential organ failure assessment (SOFA) score associated with radiographic imaging identified by tomography and/or thorax radiography, suggesting pulmonary damage due to infection
Healthy controls were subjected to peripheral blood and bronchoalveolar lavage (BAL) fluid sampling, most of the parameters displayed by these patients were not applicable for these controls

Summary

Introduction

Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection (as per the Third International Consensus definition for sepsis and septic shock) [1,2].Currently, sepsis is the tenth leading cause of death in high-income countries, accounting for more than 210,000 annual deaths in the USA [3]. Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection (as per the Third International Consensus definition for sepsis and septic shock) [1,2]. Sepsis may progress to severe sepsis with the development of further complications such as multiple organ failure (MOF) [6]. These patients have an increased risk of subsequently advancing into septic shock—a state of persistent hypotension despite intravenous fluid resuscitation due to acute circulatory failure. Both MOF and septic shock lead to eventual death [5,6]. The pathogenesis of sepsis and the contribution of cellular mediators of the inflammatory response remain poorly understood

Objectives

Results

Conclusion