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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Darrabie, MD; Cheeseman, J; Limkakeng, AT; Borawski, J; Sullenger, BA; Elster, EA; Kirk, AD; Lee, J

Published Date

  • November 2018

Published In

Volume / Issue

  • 231 /

Start / End Page

  • 270 - 277

PubMed ID

  • 30278940

Pubmed Central ID

  • 30278940

Electronic International Standard Serial Number (EISSN)

  • 1095-8673

Digital Object Identifier (DOI)

  • 10.1016/j.jss.2018.05.059

Language

  • eng

Conference Location

  • United States