Systemic inflammatory response syndrome after major abdominal surgery predicted by early upregulation of TLR4 and TLR5

Lahiri, Rajiv and Derwa, Yannick and Bashir, Zora and Giles, Edward and Torrance, Hew D. T. and Owen, Helen C. and O'Dwyer, Michael J. and O'Brien, Alastair and Stagg, Andrew J. and Bhattacharya, Satyajit and Foster, Graham R. and Alazawi, William (2016) Systemic inflammatory response syndrome after major abdominal surgery predicted by early upregulation of TLR4 and TLR5. Annals of surgery, 263 (5). pp. 1028-1037. ISSN 0003-4932

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Abstract

OBJECTIVES

To study innate immune pathways in patients undergoing hepatopancreaticobiliary surgery to understand mechanisms leading to enhanced inflammatory responses and identifying biomarkers of adverse clinical consequences.

BACKGROUND

Patients undergoing major abdominal surgery are at risk of life-threatening systemic inflammatory response syndrome (SIRS) and sepsis. Early identification of at-risk patients would allow tailored postoperative care and improve survival.

METHODS

Two separate cohorts of patients undergoing major hepatopancreaticobiliary surgery were studied (combined n = 69). Bloods were taken preoperatively, on day 1 and day 2 postoperatively. Peripheral blood mononuclear cells and serum were separated and immune phenotype and function assessed ex vivo.

RESULTS

Early innate immune dysfunction was evident in 12 patients who subsequently developed SIRS (postoperative day 6) compared with 27 who did not, when no clinical evidence of SIRS was apparent (preoperatively or days 1 and 2). Serum interleukin (IL)-6 concentration and monocyte Toll-like receptor (TLR)/NF-κB/IL-6 functional pathways were significantly upregulated and overactive in patients who developed SIRS (P < 0.0001). Interferon α-mediated STAT1 phosphorylation was higher preoperatively in patients who developed SIRS. Increased TLR4 and TLR5 gene expression in whole blood was demonstrated in a separate validation cohort of 30 patients undergoing similar surgery. Expression of TLR4/5 on monocytes, particularly intermediate CD14CD16 monocytes, on day 1 or 2 predicted SIRS with accuracy 0.89 to 1.0 (areas under receiver operator curves).

CONCLUSIONS

These data demonstrate the mechanism for IL-6 overproduction in patients who develop postoperative SIRS and identify markers that predict patients at risk of SIRS 5 days before the onset of clinical signs.

Item Type: Article
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 19097
Notes on copyright: This is a non-final version of an article published in final form in Longbottom, E.R. et al., 2016. Features of Postoperative Immune Suppression Are Reversible With Interferon Gamma and Independent of Interleukin-6 Pathways. Annals of Surgery, 264(2), pp.370–377. Available at: http://dx.doi.org/10.1097/sla.0000000000001484.
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Depositing User: Helen Roberts
Date Deposited: 08 Apr 2016 11:19
Last Modified: 05 Sep 2018 17:52
URI: http://eprints.mdx.ac.uk/id/eprint/19097

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