Evaluation of the Relationship of Neutrophil Functions With Sepsis and Septic Shock Using the Leukocyte ImmunoTest™ in Patients With Various Infectious Conditions

Introduction:

Sepsis is defined as the dysregulated host response to infection leading to organ dysfunction. Both sepsis and septic shock are important health problems affecting millions of people, resulting in a serious mortality rate around the world every year. Delay in both diagnosis and initiation of appropriate treatment are the most important causes of sepsis-related mortality. On the other hand, overdiagnosis of sepsis and initiation of broad-spectrum antibiotic therapy inappropriately have some consequences such as increased hospital costs, antibiotic-related side effects, increased antibiotic resistance, and the development of resistant nosocomial infections. To make this precise distinction, a large number of biomarkers have been studied until today. The expected benefit of sepsis-related biomarkers is the detection of infection and sepsis, the potential to predict the course of sepsis, or treatment guidance. Although there are more than 150 biomarkers studied on this subject, there is not a single biomarker that meets these expectations in all aspects in clinical practice.

Neutrophils play a vital role in the development of the host response in sepsis. Neutrophils operate using a number of different mechanisms including chemotaxis, phagocytosis, release of reactive oxygen species (ROS) and granular proteins, and the production and liberation of cytokines for this purpose. A controlled neutrophil response is required to combat infections. Recently a functional assay that assesses the capacity of leukocytes (primarily neutrophils) to produce ROS in response to in vitro chemical stimulation has been demonstrated. The Leukocyte ImmunoTest™ (LIT™) specifically and rapidly (10 minutes) quantifies neutrophil ROS release using a small volume of blood obtainable from capillary, arterial or venous sources. As such the LIT score provides a physiologically relevant means for monitoring the cellular capacity of neutrophils to produce superoxide radicals in real time. An objective marker of cellular dysfunction of neutrophils would be a helpful tool for the clinician in detecting and monitoring changes related to infection status and to determine development of sepsis and positive effects of interventions.

Method:

The study was conducted as a prospective observational study with ethical committee approval in a medical intensive care unit and inward belong to internal disease department of a university hospital. The patient population is consisted of patients who were admitted to the ICU or inward due various infectious etiologies. The control group is consisted of outpatients or inpatients admitted to ICU or inward for noninfectious etiologies. ROS production in response to PMA was performed on clinical samples and analysed within 30 minutes of collection. The LIT test was performed every day or every other day for patient group until death or discharge from units where the study is conducted. The LIT test was performed only once for outpatient group on day of outpatient control.