• Suzanne Flier, Arno N Concepcion, Dik Versteeg, Teus H Kappen, Imo E Hoefer, Dylan W de Lange, Gerard Pasterkamp, and Wolfgang F Buhre.
• From the Department of Anaesthesiology, University Medical Center Utrecht (UMCU), Utrecht (SF, THK), Department of Rheumatology and Clinical Immunology, UMCU, Utrecht (ANC), Department of Clinical Microbiology, Admiraal de Ruyter Ziekenhuis, Goes (DV), Division of Heart and Lung, Experimental Cardiology Laboratory, UMCU, Utrecht (IEH, GP), Department of Intensive Care Medicine and Department of Emergency Medicine, UMCU, Utrecht (DWDL) and Department of Anaesthesiology and Pain Medicine, University Medical Center Maastricht, Maastricht, the Netherlands (WFB).
• Eur J Anaesthesiol. 2015 Mar 1;32(3):177-88.

BackgroundCardiac surgery with cardiopulmonary bypass has a major impact on the congenital immune response, in which Toll-like receptors (TLRs) are the first line of defence. Decreased surface expression of TLRs and impaired monocyte responsiveness to TLR ligands occur following surgery. However, the clinical implications of this altered immune response are not clear.ObjectivesTo study cardiac surgery induced changes in perioperative TLR expression and monocyte responsiveness, and the association with postoperative inflammatory complications.DesignA prospective cohort study.SettingSingle university hospital, enrolment March to December 2007.PatientsEighty-four out of 92 patients who underwent coronary artery bypass grafting (CABG) were followed up until hospital discharge.Main Outcome MeasuresWe assessed in-vivo TLR-2 and TLR-4 expression and ex-vivo monocyte responsiveness to TLR-2 and TLR-4 ligands, measured by Pam3Cys and lipopolysaccharide (LPS)-induced interleukin (IL)-6 and IL-8, and tumour necrosis factor alpha (TNF-α) secretion until 24 h after surgery. Patients were followed to identify adverse inflammatory and infectious outcomes.ResultsMonocyte TLR expression decreased during CABG but returned to baseline after 24 h [linear mixed effects (LME) over time P < 0.0001]. Monocyte responsiveness changed significantly over time, with marked postoperative hyporesponsiveness (LME P < 0.0001). Decreased monocyte responsiveness to LPS was associated with monocyte TLR-4 expression (LME for IL-6 P = 0.04, IL-8 P = 0.002, TNF-α P = 0.05). Intraoperative decrease of monocyte TLR-2 expression was associated with postoperative systemic inflammatory response syndrome (SIRS) and pneumonia [odds ratio (OR) 2.06, 95% confidence interval (95% CI) 1.14 to 3.72], but the perioperative decrease of monocyte TLR-4 expression was not (OR 1.10, 95% CI 0.80 to 1.52).ConclusionCABG surgery induced a decrease in in-vivo monocyte TLR expression and also in ex-vivo monocyte responsiveness, with which monocyte TLR-4 expression and monocyte LPS responsiveness seemed to be associated. Decreased TLR-2 expression was associated with the occurrence of SIRS and pneumonia, suggesting a role in the cause of postoperative inflammatory conditions.RegistrationClinicaltrials.gov identifier: NCT00356746.

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