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Elevations in Tumor Necrosis Factor Alpha and Interleukin 6 From Neuronal-Derived Extracellular Vesicles in Repeated Low-Level Blast Exposed Personnel

OBJECTIVE: The purpose of this pilot study was to determine if military service members with histories of hundreds to thousands of low-level blast exposures (i. e., experienced breachers) had different levels of serum and neuronal-derived extracellular vesicle (EV) concentrations of interleukin (IL)...

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Autores principales: Edwards, Katie A., Leete, Jacqueline J., Smith, Ethan G., Quick, Alycia, Modica, Claire M., Wassermann, Eric M., Polejaeva, Elena, Dell, Kristine C., LoPresti, Matthew, Walker, Peter, O'Brien, Meghan, Lai, Chen, Qu, Bao-Xi, Devoto, Christina, Carr, Walter, Stone, James R., Ahlers, Stephen T., Gill, Jessica M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070565/
https://www.ncbi.nlm.nih.gov/pubmed/35528741
http://dx.doi.org/10.3389/fneur.2022.723923
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author Edwards, Katie A.
Leete, Jacqueline J.
Smith, Ethan G.
Quick, Alycia
Modica, Claire M.
Wassermann, Eric M.
Polejaeva, Elena
Dell, Kristine C.
LoPresti, Matthew
Walker, Peter
O'Brien, Meghan
Lai, Chen
Qu, Bao-Xi
Devoto, Christina
Carr, Walter
Stone, James R.
Ahlers, Stephen T.
Gill, Jessica M.
author_facet Edwards, Katie A.
Leete, Jacqueline J.
Smith, Ethan G.
Quick, Alycia
Modica, Claire M.
Wassermann, Eric M.
Polejaeva, Elena
Dell, Kristine C.
LoPresti, Matthew
Walker, Peter
O'Brien, Meghan
Lai, Chen
Qu, Bao-Xi
Devoto, Christina
Carr, Walter
Stone, James R.
Ahlers, Stephen T.
Gill, Jessica M.
author_sort Edwards, Katie A.
collection PubMed
description OBJECTIVE: The purpose of this pilot study was to determine if military service members with histories of hundreds to thousands of low-level blast exposures (i. e., experienced breachers) had different levels of serum and neuronal-derived extracellular vesicle (EV) concentrations of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNFα), compared to matched controls, and if these biomarkers related to neurobehavioral symptoms. METHODS: Participants were experienced breachers (n = 20) and matched controls without blast exposures (n = 14). Neuronal-derived EVs were isolated from serum and identified with mouse anti-human CD171. Serum and neuronal-derived EVs were analyzed for IL-6, IL-10, and TNFα using an ultra-sensitive assay. RESULTS: Serum TNFα concentrations were decreased in breachers when compared to control concentrations (p < 0.01). There were no differences in serum concentrations of IL-6, IL-10, or the IL-6/IL-10 ratio between breachers and controls (p's > 0.01). In neuronal-derived EVs, TNFα and IL-6 levels were increased in breachers compared to controls (p's < 0.01), and IL-10 levels were decreased in the breacher group compared to controls (p < 0.01). In breachers the IL-6/IL-10 ratio in neuronal-derived EVs was higher compared to controls, which correlated with higher total Rivermead Post-concussion Questionnaire (RPQ) scores (p's < 0.05). CONCLUSIONS: These findings suggest that exposure of personnel to high numbers of low-level blast over a career may result in enduring central inflammation that is associated with chronic neurological symptoms. The data also suggest that peripheral markers of inflammation are not necessarily adequate surrogates for central neuroinflammation.
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spelling pubmed-90705652022-05-05 Elevations in Tumor Necrosis Factor Alpha and Interleukin 6 From Neuronal-Derived Extracellular Vesicles in Repeated Low-Level Blast Exposed Personnel Edwards, Katie A. Leete, Jacqueline J. Smith, Ethan G. Quick, Alycia Modica, Claire M. Wassermann, Eric M. Polejaeva, Elena Dell, Kristine C. LoPresti, Matthew Walker, Peter O'Brien, Meghan Lai, Chen Qu, Bao-Xi Devoto, Christina Carr, Walter Stone, James R. Ahlers, Stephen T. Gill, Jessica M. Front Neurol Neurology OBJECTIVE: The purpose of this pilot study was to determine if military service members with histories of hundreds to thousands of low-level blast exposures (i. e., experienced breachers) had different levels of serum and neuronal-derived extracellular vesicle (EV) concentrations of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNFα), compared to matched controls, and if these biomarkers related to neurobehavioral symptoms. METHODS: Participants were experienced breachers (n = 20) and matched controls without blast exposures (n = 14). Neuronal-derived EVs were isolated from serum and identified with mouse anti-human CD171. Serum and neuronal-derived EVs were analyzed for IL-6, IL-10, and TNFα using an ultra-sensitive assay. RESULTS: Serum TNFα concentrations were decreased in breachers when compared to control concentrations (p < 0.01). There were no differences in serum concentrations of IL-6, IL-10, or the IL-6/IL-10 ratio between breachers and controls (p's > 0.01). In neuronal-derived EVs, TNFα and IL-6 levels were increased in breachers compared to controls (p's < 0.01), and IL-10 levels were decreased in the breacher group compared to controls (p < 0.01). In breachers the IL-6/IL-10 ratio in neuronal-derived EVs was higher compared to controls, which correlated with higher total Rivermead Post-concussion Questionnaire (RPQ) scores (p's < 0.05). CONCLUSIONS: These findings suggest that exposure of personnel to high numbers of low-level blast over a career may result in enduring central inflammation that is associated with chronic neurological symptoms. The data also suggest that peripheral markers of inflammation are not necessarily adequate surrogates for central neuroinflammation. Frontiers Media S.A. 2022-04-21 /pmc/articles/PMC9070565/ /pubmed/35528741 http://dx.doi.org/10.3389/fneur.2022.723923 Text en Copyright © 2022 Edwards, Leete, Smith, Quick, Modica, Wassermann, Polejaeva, Dell, LoPresti, Walker, O'Brien, Lai, Qu, Devoto, Carr, Stone, Ahlers and Gill. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Edwards, Katie A.
Leete, Jacqueline J.
Smith, Ethan G.
Quick, Alycia
Modica, Claire M.
Wassermann, Eric M.
Polejaeva, Elena
Dell, Kristine C.
LoPresti, Matthew
Walker, Peter
O'Brien, Meghan
Lai, Chen
Qu, Bao-Xi
Devoto, Christina
Carr, Walter
Stone, James R.
Ahlers, Stephen T.
Gill, Jessica M.
Elevations in Tumor Necrosis Factor Alpha and Interleukin 6 From Neuronal-Derived Extracellular Vesicles in Repeated Low-Level Blast Exposed Personnel
title Elevations in Tumor Necrosis Factor Alpha and Interleukin 6 From Neuronal-Derived Extracellular Vesicles in Repeated Low-Level Blast Exposed Personnel
title_full Elevations in Tumor Necrosis Factor Alpha and Interleukin 6 From Neuronal-Derived Extracellular Vesicles in Repeated Low-Level Blast Exposed Personnel
title_fullStr Elevations in Tumor Necrosis Factor Alpha and Interleukin 6 From Neuronal-Derived Extracellular Vesicles in Repeated Low-Level Blast Exposed Personnel
title_full_unstemmed Elevations in Tumor Necrosis Factor Alpha and Interleukin 6 From Neuronal-Derived Extracellular Vesicles in Repeated Low-Level Blast Exposed Personnel
title_short Elevations in Tumor Necrosis Factor Alpha and Interleukin 6 From Neuronal-Derived Extracellular Vesicles in Repeated Low-Level Blast Exposed Personnel
title_sort elevations in tumor necrosis factor alpha and interleukin 6 from neuronal-derived extracellular vesicles in repeated low-level blast exposed personnel
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070565/
https://www.ncbi.nlm.nih.gov/pubmed/35528741
http://dx.doi.org/10.3389/fneur.2022.723923
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