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

Publication ,  Journal Article
Darrabie, MD; Cheeseman, J; Limkakeng, AT; Borawski, J; Sullenger, BA; Elster, EA; Kirk, AD; Lee, J
Published in: J Surg Res
November 2018

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.

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Published In

J Surg Res

DOI

EISSN

1095-8673

Publication Date

November 2018

Volume

231

Start / End Page

270 / 277

Location

United States

Related Subject Headings

  • Wounds and Injuries
  • Toll-Like Receptors
  • Surgery
  • Middle Aged
  • Male
  • Humans
  • HMGB1 Protein
  • Female
  • Cell Line, Tumor
  • Case-Control Studies
 

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Darrabie, M. D., Cheeseman, J., Limkakeng, A. T., Borawski, J., Sullenger, B. A., Elster, E. A., … Lee, J. (2018). Toll-like receptor activation as a biomarker in traumatically injured patients. J Surg Res, 231, 270–277. https://doi.org/10.1016/j.jss.2018.05.059
Darrabie, Marcus D., Jennifer Cheeseman, Alexander T. Limkakeng, Joseph Borawski, Bruce A. Sullenger, Eric A. Elster, Allan D. Kirk, and Jaewoo Lee. “Toll-like receptor activation as a biomarker in traumatically injured patients.J Surg Res 231 (November 2018): 270–77. https://doi.org/10.1016/j.jss.2018.05.059.
Darrabie MD, Cheeseman J, Limkakeng AT, Borawski J, Sullenger BA, Elster EA, et al. Toll-like receptor activation as a biomarker in traumatically injured patients. J Surg Res. 2018 Nov;231:270–7.
Darrabie, Marcus D., et al. “Toll-like receptor activation as a biomarker in traumatically injured patients.J Surg Res, vol. 231, Nov. 2018, pp. 270–77. Pubmed, doi:10.1016/j.jss.2018.05.059.
Darrabie MD, Cheeseman J, Limkakeng AT, Borawski J, Sullenger BA, Elster EA, Kirk AD, Lee J. Toll-like receptor activation as a biomarker in traumatically injured patients. J Surg Res. 2018 Nov;231:270–277.
Journal cover image

Published In

J Surg Res

DOI

EISSN

1095-8673

Publication Date

November 2018

Volume

231

Start / End Page

270 / 277

Location

United States

Related Subject Headings

  • Wounds and Injuries
  • Toll-Like Receptors
  • Surgery
  • Middle Aged
  • Male
  • Humans
  • HMGB1 Protein
  • Female
  • Cell Line, Tumor
  • Case-Control Studies