Acute Inflammation in Traumatic Brain Injury and Polytrauma Patients Using Network Analysis.

introductionTraumatic brain injury (TBI) is associated with secondary injury to the central nervous system (CNS) via inflammatory mechanisms. The combination of polytrauma and TBI further exacerbates the inflammatory response to injury; however, combined injury phenomena have not been thoroughly studied. In this study, we examined the inflammatory differences between patients with TBI versus patients with polytrauma, but no TBI (polytrauma). We hypothesize that patients with TBI have a heightened early inflammatory response compared with polytrauma.

methodsWe conducted a single-center retrospective study of a cohort of patients with polytrauma, who were enrolled in the PROPPR study. These patients had blood samples prospectively collected at eight time points in the first 3 days of admission. Using radiological data to determine TBI, our polytrauma cohort was dichotomized into TBI (n = 30) or polytrauma (n = 54). Inflammatory biomarkers were measured using ELISA. Data across time were compared for TBI versus polytrauma groups using Wilcoxon rank-sum test. Network analysis techniques were used to systematically characterize the inflammatory responses at admission.

resultsPatients with TBI (51.6%) had a higher 30-day mortality compared with polytrauma (16.9%) (P <0.001). Expression levels of IL6, IL8, and CCL2 were elevated from the 2-h through 24-h time points, becoming significant at the 6-h time point (IL6, IL8, and CCL2; P <0.05) (). CSF3 showed a similar pattern, but did not attain significance. TBI and polytrauma networks underwent diverging trends from admission to the 6-h time point.

conclusionPatients with TBI demonstrated upregulations in proinflammatory cytokines IL6, IL8, and CCL2. Utilizing informatics methods, we were able to identify temporal differences in network trends, as well as uncharacterized cytokines and chemokines in TBI. These data suggest TBI induces a distinct inflammatory response and pathologically heightened inflammatory response in the presence of polytrauma and may propagate worsened patient outcomes including mortality.