Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study

Abstract

Background

Almost all studies that have investigated the immune response to trauma have analysed blood samples acquired post-hospital admission. Thus, we know little of the immune status of patients in the immediate postinjury phase and how this might influence patient outcomes. The objective of this study was therefore to comprehensively assess the ultra-early, within 1-hour, immune response to trauma and perform an exploratory analysis of its relationship with the development of multiple organ dysfunction syndrome (MODS).

Methods and findings

The immune and inflammatory response to trauma was analysed in 89 adult trauma patients (mean age 41 years, range 18–90 years, 75 males) with a mean injury severity score (ISS) of 24 (range 9–66), from whom blood samples were acquired within 1 hour of injury (mean time to sample 42 minutes, range 17–60 minutes). Within minutes of trauma, a comprehensive leukocytosis, elevated serum pro- and anti-inflammatory cytokines, and evidence of innate cell activation that included neutrophil extracellular trap generation and elevated surface expression of toll-like receptor 2 and CD11b on monocytes and neutrophils, respectively, were observed. Features consistent with immune compromise were also detected, notably elevated numbers of immune suppressive CD16 ^BRIGHT CD62L ^DIM neutrophils (82.07 x 10 ⁶/l ± 18.94 control versus 1,092 x 10 ⁶/l ± 165 trauma, p < 0.0005) and CD14 ⁺HLA-DR ^low/− monocytes (34.96 x 10 ⁶/l ± 4.48 control versus 95.72 x 10 ⁶/l ± 8.0 trauma, p < 0.05) and reduced leukocyte cytokine secretion in response to lipopolysaccharide stimulation. Exploratory analysis via binary logistic regression found a potential association between absolute natural killer T (NKT) cell numbers and the subsequent development of MODS. Study limitations include the relatively small sample size and the absence of data relating to adaptive immune cell function.

Conclusions

Our study highlighted the dynamic and complex nature of the immune response to trauma, with immune alterations consistent with both activation and suppression evident within 1 hour of injury. The relationship of these changes, especially in NKT cell numbers, to patient outcomes such as MODS warrants further investigation.

Abstract

In this prospective cohort study, Jon Hazeldine and colleagues investigate the immune and inflammatory response of trauma patients immediately after and in the hours and days following injury.

Author summary

Why was this study done?

• Whilst it is recognised that traumatic injury elicits a profound immune and inflammatory response, our knowledge is based almost entirely upon the analysis of blood samples acquired from patients post-hospital admission.

• Very little is known with regards to the immune and inflammatory status of trauma patients in the immediate aftermath of injury, thereby limiting our ability to determine factors influencing patient outcome, stratification for treatment, and the development of novel therapeutics.

• This study was undertaken to provide information on the ultra-early immune and inflammatory response that occurs within minutes of traumatic injury.

What did the researchers do and find?

• We analysed the composition and function of immune cells and the concentrations of cytokines in peripheral blood samples acquired from 89 adult trauma patients within 1 hour of injury as well as 4–12 and 48–72 hours postinjury.

• We found traumatic injury resulted in immediate immune dysfunction, with evidence of concomitant immune activation and suppression detected within minutes of injury.

• Our work uncovered a dynamic nature to the very early post-trauma immune response, revealing that certain features detected in blood samples acquired within minutes of injury were absent from subsequent samples obtained in the hours and days post-trauma.

What do these findings mean?

• Immune cell activation and the generation of inhibitory cells occur within minutes of injury, supporting the notion of a concomitant induction of immune activation and suppression immediately after trauma.

• The complex nature of the acute immune response to injury suggests that targeting 1 element of the immune response is unlikely to reduce immuneparesis or the incidence of multiple organ dysfunction syndrome (MODS).