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Toll-like receptor activation as a biomarker in traumatically injured patients

dc.contributor.author Lee, Jaewoo
dc.contributor.author Limkakeng, Alexander
dc.contributor.author Sullenger, Bruce
dc.contributor.author Borawski, Joseph
dc.contributor.author Kirk, Allan
dc.contributor.author Darrabie, MD
dc.contributor.author Cheeseman, J
dc.contributor.author Elster, EA
dc.date.accessioned 2018-08-01T23:14:12Z
dc.date.available 2018-08-01T23:14:12Z
dc.date.issued 2018-11-01
dc.identifier.issn 0022-4804
dc.identifier.issn 1095-8673
dc.identifier.uri https://hdl.handle.net/10161/17305
dc.description.abstract © 2018 Elsevier Inc. Background: Surgical insult and trauma have been shown to cause dysregulation of the immune and inflammatory responses. Interaction of damage-associated molecular patterns (DAMPs) with toll-like receptors (TLRs) initiates innate immune response and systemic inflammatory responses. Given that surgical patients produce high levels of circulating damage-associated molecular patterns, we hypothesized that plasma-activated TLR activity would be correlated to injury status and could be used to predict pathological conditions involving tissue injury. Methods: An observational study was performed using samples from a single-institution prospective tissue and data repository from a Level-1 trauma center. In vitro TLR 2, 3, 4, and 9 activation was determined in a TLR reporter assay after isolation of plasma from peripheral blood. We determined correlations between plasma-activated TLR activity and clinical course measures of severity. Results: Eighteen patients were enrolled (median Injury Severity Score 15 [interquartile range 10, 23.5]). Trauma resulted in significant elevation in circulation high mobility group box 1 as well as increase of plasma-activated TLR activation (2.8-5.4-fold) compared to healthy controls. There was no correlation between circulating high mobility group box 1 and trauma morbidity; however, the plasma-activated TLR activity was correlated with acute physiology and chronic health evaluation II scores (R square = 0.24-0.38, P < 0.05). Patients who received blood products demonstrated significant increases in the levels of plasma-activated TLRs 2, 3, 4, and 9 and had a trend toward developing systemic inflammatory response syndrome. Conclusions: Further studies examining TLR modulation and signaling in surgical patients may assist in predictive risk modeling and reduction in morbidity and mortality.
dc.relation.ispartof Journal of Surgical Research
dc.relation.isversionof 10.1016/j.jss.2018.05.059
dc.title Toll-like receptor activation as a biomarker in traumatically injured patients
dc.type Journal article
dc.date.updated 2018-08-01T23:14:11Z
pubs.begin-page 270
pubs.end-page 277
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Surgery, Emergency Medicine
pubs.organisational-group Surgery
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Basic Science Departments
pubs.organisational-group Pharmacology & Cancer Biology
pubs.organisational-group Surgery, Surgical Sciences
pubs.organisational-group Immunology
pubs.organisational-group Pediatrics
pubs.organisational-group Surgery, Abdominal Transplant Surgery
pubs.publication-status Accepted
pubs.volume 231


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