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Young and Aged Blunt Trauma Patients Display Major Differences in Circulating Inflammatory Mediator Profiles after
Ashley J Lamparello1, Rami A Namas2, Othman Abdul-Malak1
1Department of Surgery, University of Pittsburgh, Pittsburgh, PA.
Insights
Aging trauma patients show distinct inflammatory profiles, with higher levels of specific chemokines (CXCL10, CXCL9) and complex networks, not just suppressed inflammation.
Area of Science:
- Immunology
- Trauma Research
- Gerontology
Background:
- Aging alters immune function, impacting inflammatory responses.
- The inflammatory mediator network post-severe trauma in aged individuals is not well understood.
- Severe trauma triggers complex immune responses that may differ significantly with age.
Purpose of the Study:
- To compare time-dependent changes in inflammatory biomarkers and network expression in young versus aged trauma patients.
- To characterize age-related differences in circulating inflammatory mediators after severe blunt trauma.
- To investigate the complexity of inflammatory networks in young and aged trauma cohorts.
Main Methods:
- Analysis of 30 inflammatory biomarkers in plasma from young and aged blunt trauma patients.
- Plasma samples collected multiple times within the first 24 hours and daily for 7 days.
- Statistical analysis including 2-way ANOVA, AUC, Dynamic Bayesian Network, and Dynamic Network Analysis on matched cohorts.
Main Results:
- Younger trauma patients had higher Injury Severity Scores and elevated levels of 18 inflammatory mediators.
- Aged trauma patients exhibited higher levels of C-X-C motif chemokine ligand 10 (CXCL10) and C-X-C motif chemokine ligand 9 (CXCL9).
- Matched cohorts confirmed persistent higher CXCL10 and CXCL9 levels in aged individuals, with greater network complexity.
Conclusions:
- Age-related inflammatory responses to trauma are characterized by a shift in mediator profiles, not just suppressed inflammation.
- Specific chemokines like CXCL10 and CXCL9 are key mediators in aged trauma patients.
- Inflammatory network complexity increases with age following severe trauma.
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.
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