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Plasma interleukin responses as predictors of outcome stratification in patients after major trauma: a prospective observational two centre study

Jones, Matthew Allan; Hanison, James; Apreutesei, Renata; Allarakia, Basmah; Namvar, Sara; Ramaswamy, Deepa Shruthi; Horner, Daniel; Smyth, Lucy; Body, Richard; Columb, Malachy; Nirmalan, Mahesan; Nirmalan, Niroshini

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Authors

James Hanison

Renata Apreutesei

Basmah Allarakia

Deepa Shruthi Ramaswamy

Daniel Horner

Lucy Smyth

Richard Body

Malachy Columb

Mahesan Nirmalan



Abstract

Background and objectives: There is a need to develop objective risk stratification tools to define efficient care pathways for trauma patients. Biomarker-based point of care testing may strengthen existing clinical tools currently available for this purpose. The dysregulation of pro- and anti-inflammatory cytokines in the pathogenesis of organ failure is well recognised. This study was carried out to evaluate whether blood concentrations of IL-6, IL-10, and IL-6:IL-10 ratios in the early stages of the illness are significantly different in patients with worsening organ function. Materials and methods: In this prospective observational cohort study, plasma concentrations of IL-6 and IL-10 on days 1, 3 and 5 were measured in 91 major trauma patients using a multiplexed cytometric bead array approach. A composite measure of adverse outcome - defined as SOFA ≥ 2 or mortality at 7 days, was the primary outcome. IL-6 and IL-10 concentrations in early samples (days 1, 3 & 5) in patients who developed SOFA ≥ 2 on day 7 were compared against those who did not. Similar composite outcome groups at day 5 and in groups with worsening or improving SOFA scores (ΔSOFA) at days 7 and 5 were undertaken as secondary analyses. Results: Stratification on day 7, 44 (48%) patients showed adverse outcomes. These adverse outcomes associated with significantly greater IL-6 concentrations on days 1 and 5 (Day 1: 47.65 [23.24-78.68] Vs 73.69 [39.93 – 118.07] pg/mL, P = 0.040 and Day 5: 12.85 [5.80-19.51] Vs 28.90 [8.78-74.08] pg/mL; P = 0.0019). Similarly, IL-10 levels were significantly greater in the adverse outcome group on days 3 and 5 (Day 3: 2.54 [1.76-3.19] Vs 3.16 [2.68-4.21] pg/mL; P = 0.044 and Day 5: 2.03 [1.65-2.55] Vs 2.90 [2.00-5.06] pg/mL; P <0.001). IL-6 and IL-10 concentrations were also significantly elevated in the adverse outcome groups at day 3 and day 5 when stratified on day 5 outcomes. Both IL-6 and IL-6:IL-10 were found to be significantly elevated on days 1 and 3 when stratified based on ΔSOFA at day 5. This significance was lost when stratified on day 7 scores. Conclusions: Early IL-6 and IL-10 concentrations are significantly greater in patients who develop worsening organ functions downstream. These differences may provide an alternate biomarker-based approach to strengthen risk stratification in trauma patients.

Citation

Jones, M. A., Hanison, J., Apreutesei, R., Allarakia, B., Namvar, S., Ramaswamy, D. S., …Nirmalan, N. (2023). Plasma interleukin responses as predictors of outcome stratification in patients after major trauma: a prospective observational two centre study. Frontiers in Immunology, 14, 1276171. https://doi.org/10.3389/fimmu.2023.1276171

Journal Article Type Article
Acceptance Date Nov 8, 2023
Online Publication Date Nov 23, 2023
Publication Date Nov 23, 2023
Deposit Date Nov 23, 2023
Publicly Available Date Nov 27, 2023
Journal Frontiers in Immunology
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 14
Pages 1276171
DOI https://doi.org/10.3389/fimmu.2023.1276171
Keywords trauma, cytokines, biomarkers, SOFA, interleukin-6, interleukin-10
Publisher URL https://www.frontiersin.org/journals/immunology

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