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

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

Author information

1
Department of Surgery, Duke University, Durham, North Carolina.
2
Department of Surgery, Uniformed Services University of Health Sciences and Walter Reed National Military Medical Center, Bethesda, Maryland.
3
Department of Surgery, Duke University, Durham, North Carolina. Electronic address: jaewoo.lee@duke.edu.

Abstract

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

PMID:
30278940
DOI:
10.1016/j.jss.2018.05.059

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