Does Neutrophil Phenotype Predict the Survival of Trauma Patients?

Abstract

According to the World Health Organization (WHO), trauma is responsible for 10% of deaths and 16% of disabilities worldwide. This is considerably higher than those for malaria, tuberculosis, and HIV/AIDS combined. While the human suffering and death caused by injury is well-recognized, injury has a significant medical care cost. Better prediction of the state of trauma patients in the days immediately after trauma may reduce costs. Traumatic injuries to multiple organs can cause dysfunction in all systems of the body especially the immune system placing patients at high risk of infections and inflammatory complications which are often fatal. Neutrophils are the most abundant leukocyte in the human circulation and are crucial for the prevention of microbial disease. Significant changes in neutrophil functions such as enhanced chemotaxis, Neutrophil extracellular trap (NET)-induced cell death (NETosis), and phagocytosis occur early after injury followed by prolonged functional defects such as phagocytosis, killing mechanisms, and receptor expression. Analysis of these changes may improve the prediction of the patient's condition over time. We provide a comprehensive and up-to-date review of the literature investigating the effect of trauma on neutrophil phenotype with an underlying goal of using this knowledge to examine the predictive potential of neutrophil alterations on secondary complications in patients with traumatic injuries. We conclude that alterations in neutrophil surface markers and functions may be potential biomarkers that predict the outcome of trauma patients.

Keywords: injury; neutrophil subtype; neutrophils; survival; trauma.

Figure 1

The effect of trauma on neutrophil functions. During traumatic injury, damage associated molecular patterns (DAMPs) are released into the systemic circulation as a result of tissue damage. DAMPs interact with surface pattern recognition receptors (PRR), causing neutrophil recruitment which triggers many functional responses that are thought to lead to the induction of the systemic inflammatory response (SIRS) phase in trauma. These neutrophil phenotype changes include alterations in degranulation, neutrophil extracellular trap (NET) formation, cytokine production, and chemotaxis and phagocytosis.

Figure 2

Systemic inflammatory response (SIRS) and compensatory immune tolerance in trauma (CARS). Schematic diagram shows that once trauma has occurred, a primary systemic pro-inflammatory response (SIRS) is initiated which can contribute to early multi-orgn failure (MOF). The compensatory immune tolerance or anti-inflammatory response syndrome (CARS) can begin while the pro-inflammatory SIRS is still present. At the later phase CARS can lead to immune paralysis and following that, late multi organ failure [This figure is adapted from Hietbrink et al. (23)].

Figure 3

Role of neutrophils in tissue damage. Schematic illustration shows that during trauma, damage associated molecular patterns (DAMPs) are generated and these along with released mediators (ROS; NE; ARG1; hydrogen peroxide, H₂O₂, and antimicrobial proteins) recruit neutrophils to the site of injury where they release factors such as additional ROS and NE involved in the development of organ failure in a feedforward manner. Interleukin (IL)-6 and TNF-α can affect the brain causing fever in traumatic patients. Trauma-generated DAMPs also affect the liver and cause the release of inflammatory cytokines into the circulation which, in turn, further modulate neutrophil numbers and activation. DAMP, Damage-associated molecular pattern; ROS, Reactive oxygen species; PRR, pattern recognition receptor; ICAM-1, Intercellular Adhesion Molecule 1; ARG1, Arginase 1; NE, Neutrophil elastase; TNF-α, Tumor necrosis factor alpha.