Major traumatic injury : serum cytokine biomarkers as predictors of poor clinical outcome

Trauma is a leading cause of mortality and morbidity worldwide, accounting for about 5.8 million deaths annually. England alone sees approximately 25,000 cases of major trauma each year and over a fourth of these result in loss of life. Death due to trauma is time factorial and bimodally distributed. The first phase appears within an hour of injury, presenting immediate traumatic effects due to fatal injuries and haemorrhagic shocks. The second phase is marked by onset of complications after a week, characterized by further complications such as sepsis, multiple organ dysfunction and multiple organ failure. This is caused by an imbalance between pro-inflammatory and anti-inflammatory responses to traumatic injury, largely orchestrated by cytokines.Cytokines are known, to be predominantly secreted by helper T cells and activated monocytes and macrophages and numerous distinct cell types synchronize their role as part of the immune system. Each of these cell types has a distinct role in the immune system and communicates with other immune cells using secreted cytokines. Interleukins are a large class of cytokines, which are involved in systemic inflammation and immune system modulation by stimulating humoral or cell-mediated immune responses. They play an important role in fighting infection and diseases. Interleukins are also predictive biomarkers whose concentrations are measured through multiplex bioassays. The research study aims at investigating a panel of serum cytokines, cellular and metabolomic markers as a potential predictor of poor clinical outcome in major trauma. The study is a continuation of a research project with a larger cohort of 200 patients selectively recruited from Central Manchester Foundation Trust (CMFT) and Salford Royal Foundation Trust (SRFT).The aim of the study was to investigate the potential for a panel of cytokines to predict clinical outcome in patients with major traumatic injuries. This was achieved by measuring the concentrations of interleukin-13 and interleukin-17 through cytometric bead array methods on which statistical analysis was performed. The study analysis of the sub-cohort of 30 patients, investigated the role of IL-13 and IL-17 incepting single organ failure or MOF and evaluating them as candidate biomarkers for clinical prediction of good and poor outcomes. In this study, IL-13 concentration increased between day 1 and day 5, post trauma (p=0.02). Based on the Sequential organ failure assessment scores (SOFA), day 1 concentrations were compared to day 5 and day 8 at 2 different cut-offs, namely SOFA score <3 and ≥ 3 and SOFA score <6 and ≥6. This stratification showed no statistically significant differences meaning SOFA cut offs did not account for a clinical outcome prediction. Later Delta SOFA (day 5 SOFA – day 1 SOFA) was employed to assess whether the patients improved or got worse at the ICU. Though the comparison between IL-13 concentration on day 1 and delta SOFA did not show statistical significance, it revealed a weak negative relationship between them (r=-0.318, p=0.087), indicating that the patients got better at the ICU. Although IL-13 data did not show statistical significance based on SOFA, the data revealed a good clinical outcome when it was clustered tightly based on the movement of SOFA across concentrations. A percentage concentration analysis was conducted between day 1 and day 5 concentrations to show how IL-13 levels changed at different SOFA scores, and whether they could predict clinical outcome. The increase in average IL-13 concentration on D5 by 10% (3 pg/ml), tallied with decreased SOFA score, thereby indicating good clinical outcome. The analysis of IL-17 concentration showed a marginal decrease between day I and day 5 without a significant statistical difference (p=0.994). The concentration of IL-17 in day 1 was tested against SOFA score calculated for day 5 and day 8 at two different cut-offs, namely SOFA score <3 and ≥ 3 and SOFA score