title: Cardiovascular effects of tumour necrosis factor α antagonism in patients with acute myocardial infarction: a first in human study.
abstract: OBJECTIVE
  The inflammatory cytokine, tumour necrosis factor α (TNF-α), exerts deleterious cardiovascular effects. We wished to determine the effects of TNF-α antagonism on endothelial function and platelet activation in patients with acute myocardial infarction.
  A double-blind, parallel group, randomised controlled trial performed in a tertiary referral cardiac centre. 26 patients presenting with acute myocardial infarction randomised to receive an intravenous infusion of etanercept (10 mg) or saline placebo.
  
  
  METHODS
  Leucocyte count, plasma cytokine concentrations, flow cytometric measures of platelet activation and peripheral vasomotor and fibrinolytic function were determined before and 24 h after study intervention.
  
  
  RESULTS
  Consistent with effective conjugation of circulating TNF-α, plasma TNF-α concentrations increased in all patients following etanercept (254 ± 15 vs 0.12 ± 0.02 pg/ml; p < 0.0001), but not saline infusion. Etanercept treatment reduced neutrophil (7.4 ± 0.6 vs 8.8 ± 0.6 × 10(9) cells/l; p = 0.03) and plasma interleukin-6 concentrations (5.8 ± 2.0 vs 10.6 ± 4.0 pg/ml; p = 0.012) at 24 h but increased platelet-monocyte aggregation (30 ± 5 vs 20 ± 3%; p = 0.02). Vasodilatation in response to substance P, acetylcholine and sodium nitroprusside, and acute tissue plasminogen activator release were unaffected by either treatment (p > 0.1 for all).
  
  
  CONCLUSIONS
  Following acute myocardial infarction, etanercept reduces systemic inflammation but increases platelet activation without affecting peripheral vasomotor or fibrinolytic function. We conclude that TNF-α antagonism is unlikely to be a beneficial therapeutic strategy in patients with acute myocardial infarction.
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. gareth.padfield@nhs.net
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Padfield
authors.forename: Jehangir N
authors.initials: JN
authors.lastname: Din
authors.forename: Elena
authors.initials: E
authors.lastname: Koushiappi
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Mills
authors.forename: Simon D
authors.initials: SD
authors.lastname: Robinson
authors.forename: Nicholas Le May
authors.initials: Nle M
authors.lastname: Cruden
authors.forename: Andrew John
authors.initials: AJ
authors.lastname: Lucking
authors.forename: Stanley
authors.initials: S
authors.lastname: Chia
authors.forename: Scott A
authors.initials: SA
authors.lastname: Harding
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
mesh_terms: D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D000068800:Etanercept; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology*; D015539:Platelet Activation / Q000187:drug effects*; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept
keywords: MYOCARDIAL ISCHAEMIA AND INFARCTION (IHD)