@article{738b0e3262474d7383dba0cf522a3735,
title = "Elevations in Tumor Necrosis Factor Alpha and Interleukin 6 From Neuronal-Derived Extracellular Vesicles in Repeated Low-Level Blast Exposed Personnel",
abstract = "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.",
keywords = "blast, breacher, extracellular vesicles, military, neuroinflammation",
author = "Edwards, {Katie A.} and Leete, {Jacqueline J.} and Smith, {Ethan G.} and Alycia Quick and Modica, {Claire M.} and Wassermann, {Eric M.} and Elena Polejaeva and Dell, {Kristine C.} and Matthew LoPresti and Peter Walker and Meghan O'Brien and Chen Lai and Qu, {Bao Xi} and Christina Devoto and Walter Carr and Stone, {James R.} and Ahlers, {Stephen T.} and Gill, {Jessica M.}",
note = "Funding Information: This work was funded by the Joint Program Committee-5 Development of Exposure Standards to Repeated Blast Exposure program, work unit #603115HP-3730-001-A1118. This work was also supported by National Institute of Nursing Research (NINR) and National Institute of Neurological Disease and Stroke (NINDS) Intramural Research Programs. This work was supported in part by an appointment to the Research Participation Program at the Walter Reed Army Institute of Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Army Medical Research and Development Command. Some of the authors are Military Service Members (or employees of the U.S. Government). This work was prepared as part of their official duties. Title 17, U.S.C., §105 provides that copyright protection under this title is not available for any work of the U.S. Government. Title 17, U.S.C., §101 defines a U.S. Government work as a work prepared by a Military Service Member or employee of the U.S. Government as part of that person's official duties. Publisher Copyright: Copyright {\textcopyright} 2022 Edwards, Leete, Smith, Quick, Modica, Wassermann, Polejaeva, Dell, LoPresti, Walker, O'Brien, Lai, Qu, Devoto, Carr, Stone, Ahlers and Gill.",
year = "2022",
month = apr,
day = "21",
doi = "10.3389/fneur.2022.723923",
language = "English",
volume = "13",
journal = "Frontiers in Neurology",
issn = "1664-2295",
}