title: Monocyte hyporesponsiveness and Toll-like receptor expression profiles in coronary artery bypass grafting and its clinical implications for postoperative inflammatory response and pneumonia: An observational cohort study.
abstract: BACKGROUND
  Cardiac 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.
  
  
  OBJECTIVE
  To study cardiac surgery induced changes in perioperative TLR expression and monocyte responsiveness, and the association with postoperative inflammatory complications.
  
  
  METHODS
  A prospective cohort study.
  
  
  METHODS
  Single university hospital, enrolment March to December 2007.
  
  
  METHODS
  Eighty-four out of 92 patients who underwent coronary artery bypass grafting (CABG) were followed up until hospital discharge.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  Monocyte 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).
  
  
  CONCLUSIONS
  CABG 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.
  
  
  BACKGROUND
  Clinicaltrials.gov identifier: NCT00356746.
authors.affiliation: 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).
authors.forename: Suzanne
authors.initials: S
authors.lastname: Flier
authors.forename: Arno N
authors.initials: AN
authors.lastname: Concepcion
authors.forename: Dik
authors.initials: D
authors.lastname: Versteeg
authors.forename: Teus H
authors.initials: TH
authors.lastname: Kappen
authors.forename: Imo E
authors.initials: IE
authors.lastname: Hoefer
authors.forename: Dylan W
authors.initials: DW
authors.lastname: de Lange
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Wolfgang F
authors.initials: WF
authors.lastname: Buhre
mesh_terms: D000368:Aged; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000601:surgery*; D016207:Cytokines / Q000097:blood; D005260:Female; D006785:Hospitals, University; D006801:Humans; D008024:Ligands; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015999:Multivariate Analysis; D009426:Netherlands; D016017:Odds Ratio; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism; D011446:Prospective Studies; D012307:Risk Factors; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000097:blood / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000097:blood / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D008024:Ligands; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4