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

J Surg Res. 2018 Nov;231:270-277. doi: 10.1016/j.jss.2018.05.059. Epub 2018 Jun 23.


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.

Keywords: Damage-associated molecular pattern; HMGB1; Tissue injury; Toll-like receptor; Trauma.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Alarmins / metabolism*
  • Biomarkers / blood
  • Case-Control Studies
  • Cell Line, Tumor
  • Female
  • HMGB1 Protein / blood
  • Humans
  • Male
  • Middle Aged
  • Toll-Like Receptors / blood*
  • Wounds and Injuries / blood*


  • Alarmins
  • Biomarkers
  • HMGB1 Protein
  • HMGB1 protein, human
  • Toll-Like Receptors