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

Article

Lahiri, R., Derwa, Y., Bashir, Z., Giles, E., Torrance, H., Owen, H., O'Dwyer, M., O'Brien, A., Stagg, A., Bhattacharya, S., Foster, G. and Alazawi, W. 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. https://doi.org/10.1097/SLA.0000000000001248
TypeArticle
TitleSystemic inflammatory response syndrome after major abdominal surgery predicted by early upregulation of TLR4 and TLR5
AuthorsLahiri, R., Derwa, Y., Bashir, Z., Giles, E., Torrance, H., Owen, H., O'Dwyer, M., O'Brien, A., Stagg, A., Bhattacharya, S., Foster, G. and Alazawi, W.
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.

Keywordsmonocyte; sepsis; SIRS ; surgery; TLR
PublisherLippincott, Williams and Wilkins
JournalAnnals of Surgery
ISSN0003-4932
Electronic1528-1140
Publication dates
Print31 May 2016
Publication process dates
Deposited08 Apr 2016
Accepted27 Feb 2015
Output statusPublished
Accepted author manuscript
Copyright Statement

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.

Digital Object Identifier (DOI)https://doi.org/10.1097/SLA.0000000000001248
PubMed ID26020106
Web of Science identifierWOS:000374871600038
LanguageEnglish
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