title: Increased cytokine response after toll-like receptor stimulation in patients with stable coronary artery disease.
abstract: OBJECTIVE
  Atherosclerosis is associated with increased levels of plasma cytokines and expression of Toll-like receptors (TLRs). Yet, little is known about the potential use of TLR ligand induced cytokine release as a biomarker of coronary artery disease (CAD). In this study, we investigated whether TLR ligand induced cytokine release is associated with atherosclerotic disease severity and its predictive value for future cardiovascular events.
  
  
  METHODS
  Blood samples were obtained from 260 patients with stable angina and 15 healthy controls. Cytokine levels of TNFα, IL-8 and IL-6 were measured after 2 h of whole blood stimulation with 10 ng/ml lipopolysaccharide (LPS, TLR4 ligand) and P3C 500 ng/ml (TLR2 ligand). In a subgroup, dose-response curves were created using additional LPS concentrations.
  
  
  RESULTS
  LPS induced whole blood release of TNFα and IL-6, but not IL-8, was significantly higher in patients compared to healthy controls. Among CAD patients, TLR responses did hardly differ when associated with the presence of traditional risk factors and atherosclerotic disease severity (number of diseased vessels and coronary stenosis degree). Patients with secondary events during follow-up showed a trend towards an increased TLR response. Furthermore, positive associations were found between CRP levels and TLR-induced TNFα (CRP<2: 2055 pg/ml; CRP>2: 2364 pg/ml) and IL-6 production (CRP<2: 1742 pg/ml; CRP>2: 2250 pg/ml).
  
  
  CONCLUSIONS
  In conclusion, TLR-induced whole blood cytokine release in patients with stable angina indicates the presence of coronary atherosclerosis but does not reflect its severity.
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: E H A M
authors.initials: EH
authors.lastname: Elsenberg
authors.forename: J E M
authors.initials: JE
authors.lastname: Sels
authors.forename: M A
authors.initials: MA
authors.lastname: Hillaert
authors.forename: A H
authors.initials: AH
authors.lastname: Schoneveld
authors.forename: N A M
authors.initials: NA
authors.lastname: van den Dungen
authors.forename: T C
authors.initials: TC
authors.lastname: van Holten
authors.forename: M
authors.initials: M
authors.lastname: Roest
authors.forename: J W
authors.initials: JW
authors.lastname: Jukema
authors.forename: A J
authors.initials: AJ
authors.lastname: van Zonneveld
authors.forename: P G
authors.initials: PG
authors.lastname: de Groot
authors.forename: N
authors.initials: N
authors.lastname: Pijls
authors.forename: G
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: I E
authors.initials: IE
authors.lastname: Hoefer
mesh_terms: D000368:Aged; D060050:Angina, Stable / Q000097:blood*; D019540:Area Under Curve; D050197:Atherosclerosis; D002097:C-Reactive Protein / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000166:cytology*; D008070:Lipopolysaccharides / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D019007:P-Selectin / Q000378:metabolism; D012307:Risk Factors; D051193:Toll-Like Receptors / Q000097:blood*
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; C509295:ITGAM protein, human; D008070:Lipopolysaccharides; D019007:P-Selectin; C546937:SELP protein, human; D051193:Toll-Like Receptors; D002097:C-Reactive Protein
keywords: Atherosclerosis; Circulating cells; Coronary artery disease; Cytokines; Toll-like receptor response