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

Abstract

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 ¼ 115) and aged (65 to 90 years old, n ¼ 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 ¼ 56 young vs n ¼ 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 gammainduced 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.

A conceptual time window‐based model for the early stratification of trauma patients

“…Another ISS‐based study of stringently matched cohorts (controlling for sex ratio and age) found that patients with severe traumatic injury (ISS ≥ 25) had higher circulating levels of IL‐6, IL‐7, IL‐17, sIL‐2Rα, GM‐CSF, IP‐10/CXCL10, MIG/CXCL9 and MCP‐1/CCL2 when compared to mildly and moderately injured patients . Most recently, we demonstrated that aged patients (≥65 years old) had distinct inflammatory network patterns as compared to young patients (18–30 years old) that were not simply characterized by a suppression of pro‐inflammatory responses, but a shift in mediator patterns with high levels of CXC chemokines (IP‐10/CXCL10 and MIG/CXCL9) in the aged .…”

“… showed that upregulation of death pathways in immune cells within 2 h of injury correlated with MOF several days later. We have shown that patterns of damage‐associated molecular patterns (DAMPs), cytokines and chemokines measured on admission and over the first 24 h correlate with complications such as nosocomial infection and death and vary significantly in young vs. aged patients . The second key aspect of knowing the time of onset is the ability to define discrete time periods relative to the traumatic event.…”

Unsupervised Clustering Analysis Based on MODS Severity Identifies Four Distinct Organ Dysfunction Patterns in Severely Injured Blunt Trauma Patients

“…This may be due in part, to the range of injury severity represented within our patient cohort. For example, we have recently shown that young and old patients that had moderate severity injury experienced a similar level of MODS (38). Two age-based sub-cohorts were identified, namely young (age: 18-30 years) and aged (age: 65-90 years) matched for ISS in the moderate range.…”

Prehospital plasma is associated with distinct biomarker expression following injury

“…For example, the dysregulation of immune responses leads to worsening short-term (<24 hours) and long-term (>30 days) outcomes related to infection (16), persistent illness (17), and mortality (18). The dynamic patterns of immune mediator levels have been correlated with injury characteristics (10), patient demographics (19,20), and outcomes (16,21). Likewise, endothelial proteins such as syndecan-1 and thrombomodulin (TM) have been used to assess the degree of endothelial glycocalyx damage and to predict mortality following trauma (22)(23)(24).…”