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

Marcus D. Darrabie, Jennifer Cheeseman, Alexander T. Limkakeng, Joseph Borawski, Bruce A. Sullenger, Eric A. Elster, Allan D. Kirk, Jaewoo Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish
Pages (from-to)270-277
Number of pages8
JournalJournal of Surgical Research
StatePublished - Nov 2018
Externally publishedYes


  • Damage-associated molecular pattern
  • HMGB1
  • Tissue injury
  • Toll-like receptor
  • Trauma


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