J. Cai1, I. Billiar2, Y. Vodovotz1, T. R. Billiar1, R. A. Namas1 1University Of Pittsburgh,Pittsburgh, PA, USA 2University Of Chicago,Chicago, IL, USA
Introduction: Blunt trauma elicits a complex, multi-dimensional inflammatory response that is intertwined with late complications such as nosocomial infection and multiple organ dysfunction. Among multiple presenting factors (age and gender), the magnitude of injury severity appears to have the greatest impact on the inflammatory response which in turn correlates with clinical trajectories in trauma patients. However, a relatively limited number of inflammatory mediators have been characterized in human trauma. Here, we sought to characterize the time course changes in 31 cytokines and chemokines in a large cohort of blunt trauma patients and analyze the differences as a function of injury severity.
Methods: Using clinical and biobank data from 472 blunt trauma patients admitted to the intensive care unit (ICU) and who survived to discharge, three groups were identified based on injury severity score (ISS): Mild (ISS: 1-15, n=180), Moderate (ISS: 15-24, n=170), and Severe (ISS: ≥25, n=122). Three samples within the first 24 h were obtained from all patients and then daily up to day 7 post-injury. Thirty-one cytokines and chemokines were assayed using Luminex™ and were analyzed using Kruskal–Wallis test (P<0.05). Principal component analysis (PCA) was used to define the principal characteristics / drivers of the inflammatory response in each group.
Results: The severe group had statistically significantly longer ICU and hospital stays, days on mechanical ventilation, and higher prevalence of nosocomial infection (47%) when compared to the mild and moderate groups (16% and 24%; respectively). Time course analysis of biomarker trajectories showed that 21 inflammatory mediators were significantly higher in the severe group upon admission and over time vs the mild and moderate groups. However, 8 inflammatory mediators (IL-22, IL-9, IL-33, IL-21, IL-23, IL-17E/25, IP-10, and MIG) were significantly attenuated during the initial 16 h post-injury in the severe group when compared to the mild and moderate groups. PCA suggested that the circulating inflammatory response during the initial 16 h in the mild and moderate groups was characterized primarily by IL-13, IL-1β, IL-22, IL-9, IL-33, and IL-4. Interestingly, and over 16 h post-injury, IL-4, IL-17A, IL-13, IL-9, IL-1β, and IL-7 were the primary characteristics of the inflammatory response in the severe group.
Conclusion: These findings suggest that severe injury is associated with an early suppression of a subset of cytokines known to be involved in tissue protection and regeneration (IL-22, IL-33, IL-25 and IL-9), lymphocyte differentiation (IL-21 and IL-23) and cell trafficking (CXC chemokines) post-injury which in turn correlates with adverse clinical outcomes. Therapies targeting the immune response after injury may need to be tailored differently based on injury severity and could be personalized by the measurement of inflammatory biomarker patterns.