High IL-6 in military personnel relates to multiple traumatic brain injuries and post-traumatic stress disorder

Rodney, Tamar; Taylor, Patricia; Dunbar, Kerri; Perrin, Nancy; Lai, Chen; Roy, Michael J.; Gill, Jessica

doi:10.1016/j.bbr.2020.112715

Cited by 26 publications

(33 citation statements)

References 38 publications

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“…Studies in mild and/or recurrent TBI should also consider more subtle functional outcomes such as return to work, post-traumatic stress disorder (PTSD) and neurocognitive sequelae such as fatigue, and their relationship to IL-6 levels. One such example is the recent study by Rodney et al, indicating higher IL-6 concentrations in TBI patients suffering from long-term PTSD symptoms [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 as a prognostic biomarker of clinical outcomes after traumatic brain injury: a systematic review

et al. 2022

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Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. There are currently no early biomarkers for prognosis in routine clinical use. Interleukin-6 (IL-6) is a potential biomarker in the context of the established role of neuroinflammation in TBI recovery. Therefore, a systematic review of the literature was performed to assess and summarise the evidence for IL-6 secretion representing a useful biomarker for clinical outcomes. A multi-database literature search between January 1946 and July 2021 was performed. Studies were included if they reported adult TBI patients with IL-6 concentration in serum, cerebrospinal fluid (CSF) and/or brain parenchyma analysed with respect to functional outcome and/or mortality. A synthesis without meta-analysis is reported. Fifteen studies were included, reporting 699 patients. Most patients were male (71.7%), and the pooled mean age was 40.8 years; 78.1% sustained severe TBI. Eleven studies reported IL-6 levels in serum, six in CSF and one in the parenchyma. Five studies on serum demonstrated higher IL-6 concentrations were associated with poorer outcomes, and five showed no signification association. In CSF studies, one found higher IL-6 levels were associated with poorer outcomes, one found them to predict better outcomes and three found no association. Greater parenchymal IL-6 was associated with better outcomes. Despite some inconsistency in findings, it appears that exaggerated IL-6 secretion predicts poor outcomes after TBI. Future efforts require standardisation of IL-6 measurement practices as well as assessment of the importance of IL-6 concentration dynamics with respect to clinical outcomes, ideally within large prospective studies. Prospero registration number: CRD42021271200

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Section: Discussionmentioning

confidence: 99%

Interleukin-6 as a prognostic biomarker of clinical outcomes after traumatic brain injury: a systematic review

et al. 2022

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“…27 Therefore, the expression levels of both IL-6 and TNF-α were tested owing to their roles as important inflammatory molecules in TBIs. 28,29 The results showed that a TBI significantly increased the expression levels of IL-6 and TNF-α (p < 0.01). Compared with the TBI group, TNS treatment alleviated the increase in IL-6 and TNF-α expression levels that were induced by the TBI (p < 0.01) (Fig.…”

Section: The Effects Of Tns On Inflammation and Apoptosismentioning

confidence: 96%

The Effectiveness of Trigeminal Nerve Stimulation on Traumatic Brain Injury

Yang

Zhang

et al. 2022

Neuromodulation: Technology at the Neural Interface

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“…PTSD has been previously linked to low grade systemic inflammation, characterized by elevated blood levels of inflammatory markers (Maes et al, 1999;Passos et al, 2015;Speer et al, 2018). Chronic PTSD symptoms have been associated with peripheral blood elevations of IL-6 in civilians and military populations (Gill et al, 2010;Lindqvist et al, 2014;Rodney et al, 2020). Cytokines mediate cell-to-cell communication as soluble factors and in association with EVs, where they might be surfacebound or encapsulated (Fitzgerald et al, 2018).…”

Section: Frontiers Inmentioning

confidence: 99%

“…TBI of all severities has been associated with remote neurodegeneration, persistent inflammation, and vascular changes (Johnson et al, 2013;Woodcock and Morganti-Kossmann, 2013;Mckee and Daneshvar, 2015;Jassam et al, 2017). PTSD has been linked to inflammation and immune dysregulation, with reports of elevated peripheral blood levels of cytokines in association with PTSD symptoms in participants with TBI (Gill et al, 2010;Passos et al, 2015;O'Donovan et al, 2017;Rodney et al, 2020). Our group has previously reported correlations between PTSD symptom severity and EV levels of neurofilament light chain (NfL), a protein found in large myelinated axons and a marker of axonal injury and degeneration in military populations with a positive history of mTBI (Menke et al, 2015;Zetterberg 2016;Guedes et al, 2020a).…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicle Proteins and MicroRNAs Are Linked to Chronic Post-Traumatic Stress Disorder Symptoms in Service Members and Veterans With Mild Traumatic Brain Injury

et al. 2021

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Symptoms of post-traumatic stress disorder (PTSD) are common in military populations, and frequently associated with a history of combat-related mild traumatic brain injury (mTBI). In this study, we examined relationships between severity of PTSD symptoms and levels of extracellular vesicle (EV) proteins and miRNAs measured in the peripheral blood in a cohort of military service members and Veterans (SMs/Vs) with chronic mTBI(s). Participants (n = 144) were divided into groups according to mTBI history and severity of PTSD symptoms on the PTSD Checklist for DSM-5 (PCL-5). We analyzed EV levels of 798 miRNAs (miRNAs) as well as EV and plasma levels of neurofilament light chain (NfL), Tau, Amyloid beta (Aβ) 42, Aβ40, interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNFα), and vascular endothelial growth factor (VEGF). We observed that EV levels of neurofilament light chain (NfL) were elevated in participants with more severe PTSD symptoms (PCL-5 ≥ 38) and positive mTBI history, when compared to TBI negative controls (p = 0.024) and mTBI participants with less severe PTSD symptoms (p = 0.006). Levels of EV NfL, plasma NfL, and hsa-miR-139–5p were linked to PCL-5 scores in regression models. Our results suggest that levels of NfL, a marker of axonal damage, are associated with PTSD symptom severity in participants with remote mTBI. Specific miRNAs previously linked to neurodegenerative and inflammatory processes, and glucocorticoid receptor signaling pathways, among others, were also associated with the severity of PTSD symptoms. Our findings provide insights into possible signaling pathways linked to the development of persistent PTSD symptoms after TBI and biological mechanisms underlying susceptibility to PTSD.

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High IL-6 in military personnel relates to multiple traumatic brain injuries and post-traumatic stress disorder

Cited by 26 publications

References 38 publications

Interleukin-6 as a prognostic biomarker of clinical outcomes after traumatic brain injury: a systematic review

Interleukin-6 as a prognostic biomarker of clinical outcomes after traumatic brain injury: a systematic review

The Effectiveness of Trigeminal Nerve Stimulation on Traumatic Brain Injury

Extracellular Vesicle Proteins and MicroRNAs Are Linked to Chronic Post-Traumatic Stress Disorder Symptoms in Service Members and Veterans With Mild Traumatic Brain Injury

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