Early interleukin-6 and slope of monocyte human leukocyte antigen-DR: a powerful association to predict the development of sepsis after major trauma

Abstract

Objective: Major trauma is characterized by a pro-inflammatory response, followed by an immunosuppression. Recently, in trauma patients, the lack of recovery of monocyte Human Leukocyte Antigen DR (mHLA-DR, a biomarker of ICU-acquired immunosuppression) between days 1-2 and days 3-4 has been demonstrated to be independently associated with sepsis development. The main objective of this study was to determine whether early measurements of IL-6 (interleukin-6) and IL-10 plasma concentrations (as markers of initial severity) could improve, in association with mHLA-DR recovery, the prediction of sepsis occurrence in severe trauma patients.

Design: Prospective observational study over 24 months in a Trauma ICU at university hospital.

Patients: Trauma patients with an ISS over 25 and age over 18 were included.

Measurements and main results: mHLA-DR was assessed by flow cytometry, IL-6 and IL-10 concentrations by ELISA. 100 consecutive severely injured patients were monitored (mean ISS 37±10). 37 patients developed sepsis. IL-6 concentrations and slope of mHLA-DR expression between days 1-2 and days 3-4 were significantly different between septic and non-septic patients. IL-10 was not detectable in most patients. After adjustment for usual clinical confounders, when assessed as a pair, multivariate logistic regression analysis revealed that a slope of mHLA-DR expression (days 3-4/days 1-2)≤1.1 and a IL-6 concentration ≥ 67.1 pg/ml remained highly associated with the development of sepsis (adjusted OR 18.4, 95% CI 4.9; 69.4, p = .00002).

Conclusions: After multivariate regression logistic analysis, when assessed as a pair, a high IL-6 concentration and a persistent mHLA-DR decreased expression were found to be in relation with the development of sepsis with the best predictive value. This study underlines the usefulness of daily monitoring of immune function to identify trauma patients at a high risk of infection.

Figure 1. Time course of mHLA-DR expression in trauma patients, with (gray) or without (white bars) sepsis.

mHLA-DR is expressed as numbers of anti-HLA-DR antibodies bound per cell (AB/C). Results are expressed as mean ± standard deviation (t test, * p<.01). mHLA-DR expression was not different between the two groups at days 1–2, but was significantly lower in septic patients than in non-septic patients at days 3–4.

Figure 2. ROC curve of mHLA-DR expression slope (dash line) and IL-6 (full line) for predicting sepsis.

Area under curves for mHLA-DR slope (days 3–4 /days 1–2) and IL-6 at days 1–2 were respectively .79 (95%CI .69; .88, p = .0001) and .75 (95%CI .64; .84, p = .0001). The best threshold was 1.1 for mHLA-DR ratio (sensitivity 82.6%, specificity 64.7%) and 67.1 pg/ml for IL-6 concentration (sensitivity 84.6% and specificity 72.5%).

Figure 3. Time course of IL-6 concentration in trauma patients, with (gray) or without (white bars) sepsis.

Results (pg/ml) are expressed as median [interquartile range] (Mann & Whitney U test, * p<.01). At days 1–2, IL-6 concentration was significantly higher in septic patients than in non-septic patients, as at days 3–4 but with less significance.