Toll-like receptor activation as a biomarker in traumatically injured patients
| Autor: | Jennifer Cheeseman, Eric A. Elster, Alexander T. Limkakeng, Allan D. Kirk, Bruce A. Sullenger, Marcus D. Darrabie, Jaewoo Lee, Joseph B. Borawski |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male HMGB1 03 medical and health sciences 0302 clinical medicine Immune system Interquartile range Cell Line Tumor Medicine Alarmins Humans HMGB1 Protein Toll-like receptor Innate immune system biology business.industry Toll-Like Receptors Damage-associated molecular pattern Middle Aged 030104 developmental biology Case-Control Studies Immunology biology.protein Biomarker (medicine) Injury Severity Score Wounds and Injuries Surgery Female business Biomarkers 030215 immunology |
| Zdroj: | The Journal of surgical research. 231 |
| ISSN: | 1095-8673 |
| Popis: | 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.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.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.Further studies examining TLR modulation and signaling in surgical patients may assist in predictive risk modeling and reduction in morbidity and mortality. |
| Databáze: | OpenAIRE |
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