Polytrauma in Older Adults Leads to Significantly Increased TIMP-1 Levels in the Early Posttraumatic Period.

Mareen Braunstein,Viktoria Bogner-Flatz,Wolfgang Böcker,Wolf Mutschler,Christian Kammerlander,Thomas Kusmenkov

doi:10.1155/2020/4936374

Mareen Braunstein, Viktoria Bogner-Flatz + Show 4 more

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https://doi.org/10.1155/2020/4936374

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Abstract

Background Patients after polytrauma regularly suffer from posttraumatic immune system destabilization, which closely influences the further clinical development. Increasing age has recently been identified as an isolated risk factor for an adverse outcome after major trauma. Higher rates and intensity of acute inflammation following severe injury suggest that deregulated inflammation may contribute to these higher rates of posttraumatic morbidity and mortality in older adults. MMP-9 and TIMP-1 have been found to play a major role in posttraumatic immune disorder in a previous genome-wide mRNA analysis. Objective The aim of this study was to evaluate the differences in serum protein dynamics in older and younger polytraumatized adults. Methods Blood samples were drawn immediately within 90 minutes after trauma and subsequently after 6, 12, 24, 48, and 72 h. Serum levels of TIMP-1 and MMP-9 were quantified using ELISA. Age groups were divided according to a cutoff of 60 years. Results 60 polytrauma patients (ISS > 16) were included (<60 years, n = 49; ≥60 years, n = 49; ≥60 years, n = 11). Serum TIMP-1 and MMP-9 levels showed a highly significant serum dynamic in young and old polytrauma patients (p < 0.001). Patients ≥ 60 years showed significantly higher overall TIMP-1 levels (p < 0.001). Patients ≥ 60 years showed significantly higher overall TIMP-1 levels (p = 0.008). TIMP-1 levels showed a significant maximum after 72 h in the older study population. MMP-9 levels were nonsignificantly higher during the whole observational period in older polytrauma patients when compared to younger patients. Conclusion The posttraumatic immune response is characterized by significantly higher TIMP-1 levels in older polytrauma patients. This significant association between TIMP-1 levels and patients' age indicates a more extensive immune dysregulation following major trauma in older adults.

Highlights

Systemic immune activation and dysfunction are still a major cause of late posttraumatic morbidity and mortality [1, 2]
Increasing age has recently been identified as an isolated risk factor for an adverse outcome after major trauma
matrix metalloproteinase-9 (MMP-9) and TIMP-1 have been found to play a major role in posttraumatic immune disorder in a previous genome-wide mRNA analysis

Summary

Introduction

Systemic immune activation and dysfunction are still a major cause of late posttraumatic morbidity and mortality [1, 2]. Irrespective of major trauma, aging is associated with several physical changes including the innate immunity leading to severe dysregulation of initiation, modulation, and determination of the primary inflammatory response [7] This phenomenon is known as “inflamm-aging” and characterized by high plasma levels of circulating proinflammatory cytokines [8, 9]. Considering these facts, the combination of age-related and trauma-related immune dysregulation might contribute to higher posttraumatic morbidity and mortality in older adults [10]. The posttraumatic immune response is characterized by significantly higher TIMP-1 levels in older polytrauma patients This significant association between TIMP-1 levels and patients’ age indicates a more extensive immune dysregulation following major trauma in older adults

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