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.

Predicting the Outcomes of Subjects With Severe Community-Acquired Pneumonia Using Monocyte Human Leukocyte Antigen-DR

“…24 Meisel et al 20 and Schefold et al 25 demonstrated that awareness of the levels of mHLA-DR may help in guiding immunomodulatory therapy, shortening mechanical ventilation time and the duration of hospital stay. In recent years, several studies have shown that mHLA-DR is a valuable factor that can predict the outcomes of subjects with sepsis, severe pancreatitis, non-small cell lung cancers, cirrhosis, and secondary infections [3][4][5][6][7][8] ; some studies concluded otherwise, as the investigators suggested that mHLA-DR is not an independent factor that affects the outcomes of subjects and pointed out the limitations of flow cytometer examinations. [9][10][11] The immune system plays an important role in the development and progression of pneumonia, and mHLA-DR is a widely accepted biomarker that can reflect the immune functions.…”

“…Several studies over the past few years have demonstrated that monocyte human leukocyte antigen-DR (mHLA-DR) is a potential biomarker in predicting the outcomes of subjects with certain diseases (including sepsis, severe pancreatitis, non-small cell lung cancer, cirrhosis, and secondary infection), [3][4][5][6][7][8] although some studies have contrasting results. [9][10][11] The immune system plays an important role in the development, progression, and prognosis of pneumonia, 12 which suggests that this widely accepted immune function-related biomarker may predict outcomes in patients with severe pneumonia.…”

Predictive value of cytokines for developing complications after polytrauma

“…IL-6: (1) ARDS; two studies [37,45] could not relate ARDS to IL-6 concentration alterations, whereas two other studies [48,51] found a positive correlation (Table 2); (2) Sepsis; five studies [35,41,46,47,53] found an increased IL-6 production to be predictive for the development of sepsis, whereas five other studies [28,29,38,39,55] did not (Table 3); (3) MODS; all five prospective cohort studies [3,28,34,46,51] concluded that IL-6 is markedly increased in the early development of MODS ( Dekker ABE et al . Do cytokines predict polytrauma outcome IL-10: (1) Three studies, two prospective [54,57] and one retrospective [14] , could not relate the serum IL-10 concentrations to the development of ARDS.…”

Screening of differentially expressed genes between multiple trauma patients with and without sepsis

“…Polymorphisms of the tumor necrosis factor-encoding gene (Majetschak et al, 2002;O'Keefe et al, 2002) and interferon-gamma-encoding gene (Stassen et al, 2002) have also been investigated. Gouel-Cheron et al (2012) found that a high interleukin-6 (IL-6) concentration and a persistent decrease in monocytic human leukocyte antigen DR (mHLA-DR) expression are indicators for development of sepsis. Microarray technology allows a widely used gene expression profile method for exploring molecular mechanisms.…”