Young and Aged Blunt Trauma Patients Display Major Differences in Circulating Inflammatory Mediator Profiles after Severe Injury

Background: Aging is accompanied by alterations in immune functions. How these changes translate into levels of circulating inflammatory mediators and network expression after severe trauma is not well characterized. To address this, we compared time-dependent changes in the levels of an extensive biomarker panel in cohorts of severely injured young and aged adults. Study Design: Cohorts of young (18 to 30 years old, n = 115) and aged (65 to 90 years old, n = 101) blunt trauma patients admitted to the ICU with plasma sampled 3 times within the first 24 hours and daily from day 1 to day 7 were assayed for 30 inflammatory biomarkers using Luminex analyzer. Stringently matched groups controlling for sex ratio and Injury Severity Score (n = 56 young vs n = 56 aged) were generated. Data were analyzed using 2-way ANOVA, area under the curve analysis, Dynamic Bayesian Network inference, and Dynamic Network Analysis. Results: In the overall cohorts, the young group had a significantly higher Injury Severity Score, which was associated with higher circulating levels of 18 inflammatory mediators from admission to day 7. The aged group had higher levels of C-X-C motif chemokine ligand 10/interferon gamma-induced protein 10 and C-X-C motif chemokine ligand 9/monokine induced by gamma interferon. In groups that were matched for Injury Severity Score, the significantly higher levels of interferon gamma-induced protein 10 and monokine induced by gamma interferon persisted in the aged. Dynamic Bayesian Network revealed interferon gamma-induced protein 10 and monokine induced by gamma interferon as key mediators in the aged, and Dynamic Network Analysis revealed higher network complexity in the aged. Conclusions: These findings indicate that differences in the early inflammatory networks between young and aged trauma patients are not simply a suppression of pro-inflammatory responses in the aged, but are characterized by a major shift in the mediator profile patterns with high levels of CXC chemokines in the aged.