Interleukin-6 and Interleukin-10 concentrations as predictors of patient outcome following major traumatic injury

Jones, MA

Abstract

Trauma is one of the main causes of death worldwide, accounting for 4.8 million deaths per
year. This death rate has led to trauma being classed as the top cause of death for males,
aged between fifteen and twenty-nine. More recently, however, the pattern of major
trauma is reported to be changing, with elderly cohorts and falls from less than 2 meters
emerging as the dominant presenting complaint. In addition to these deaths, directly caused
in the early phase following major trauma, a second peak of deaths resulting from the
complications including sepsis and multiple organ failure, occurs in the days and weeks
following the initial traumatic insult.

These complications develop due to an imbalance between the pro-inflammatory and antiinflammatory
response to traumatic injury. This imbalance results in the counter
inflammatory response becoming dominant. This results in complications including sepsis
and multi-organ failure occurring due to the resultant immunosuppression. Thus, the ability
to monitor the pro- and anti-inflammatory responses through the measurement of
interleukin-6 and interleukin-10, may allow an early prediction of patient outcome and the
likelihood of developing complications.

Blood samples and clinical data were taken on days 1, 3 and 5, with additional clinical data
taken on day 8, following admission. Patient blood serum was analysed for their interleukin-
6 and interleukin-10 concentrations, using cytometric bead arrays, in sequential samples,
over a five-day period following traumatic injury.

The concentrations of interleukin-6 and interleukin-10 for these patients were then
compared to their clinical data and scoring systems. This evaluated the use of interleukin-6
or interleukin-10 as potential biomarkers for the early detection of complications and poor
clinical outcome following trauma. Metabolomic analysis was also conducted in parallel to
validate methodology and identify new molecules and pathways involved in the response to
trauma.

Interleukin-10 concentration was further utilised to cluster liquid chromatography/mass
spectrometry metabolomic analysis to identify significant metabolites that are higher in
patients with elevated interleukin-10.

Preliminary results show that both interleukin-6 and interleukin-10 differentiate between
good and poor outcome. Median interleukin-6 concentrations were found to be at their
peak in day 1 (54.28 pg/ml ± 214.48), decreasing in day 3 (29.43 pg/ml ± 300.19) and further
decreasing in day 5 (10.90 pg/ml ± 673.74). A similar pattern was observed following
analysis for interleukin-10 with the peak on day 1 (5.87 pg/ml ± 20.21), decreasing in day 3
(2.59 pg/ml ± 4.96) and decreasing further in day 5 (1.99 pg/ml ± 8.82). Furthermore, Day 1
interleukin-10 concentrations were used to cluster the metabolomic analysis. With this
grouping, a significant change in penicillin based antibiotic metabolites was observed in day
5 metabolomic analysis of trauma patient’s serum samples, identifying day 1 interleukin-10
a predictive marker for the need for long term antibiotic usage.

This study indicates that the balance between interleukin-6 and interleukin-10 has potential
predictive value for the early detection of complications following trauma and provide early
guidance towards optimal therapeutic intervention.

Citation

Jones, M. Interleukin-6 and Interleukin-10 concentrations as predictors of patient outcome following major traumatic injury. (Dissertation). University of Salford

• Thesis Type: Dissertation
• Deposit Date: Feb 23, 2018
• Publicly Available Date: Feb 23, 2018
• Award Date: Oct 1, 2017