title: The balance between pro- and anti-inflammatory cytokines is associated with platelet aggregability in acute coronary syndrome patients.
abstract: BACKGROUND
  Residual platelet reactivity (RPR) on antiplatelet therapy in ischemic heart disease patients is associated with adverse events. Clinical, cellular and pharmacogenetic factors may account for the variable response to antiplatelet treatment.
  
  
  OBJECTIVE
  We sought to explore the interplay of multiple pro-inflammatory and anti-inflammatory cytokines with platelet function in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) on dual antiplatelet therapy.
  
  
  METHODS
  In 208 ACS patients undergoing PCI on dual antiplatelet therapy we measured platelet function by platelet aggregation with two agonists [1mM arachidonic acid (AA) and 10muM ADP]. IL-1beta, IL-1ra, IL-4, IL-6, IL-8, IL-10, IL-12, IP-10, IFN-gamma, MCP-1, MIP-1alpha, MIP-1beta, TNF-alpha, and VEGF levels were determined by using the Bio-Plex cytokine assay (Bio-Rad Laboratories Inc., Hercules, CA, USA). We defined patients with RPR those with platelet aggregation by AA >or=20% and/or ADP (10micromol) >or=70%.
  
  
  RESULTS
  We documented a significant association between IP-10, IFN-gamma, IL-4 and RPR by both AA- and ADP-induced platelet aggregation after adjustment for age, sex, cardiovascular risk factors, ejection fraction, BMI, vWF and CRP. Patients with pro-inflammatory cytokines not compensated by anti-inflammatory cytokines had higher risk of RPR by both AA and ADP (AA: OR=3.85, 95% CI 1.52-9.74; ADP: OR=2.49, 95% CI 1.33-4.68) with respect to patients with balanced anti-/pro-inflammatory cytokines. Patients with anti-inflammatory response overwhelming pro-inflammatory response have lower risk of RPR (AA: OR=0.55, 95% CI 0.28-1.06; ADP: OR=0.47, 95% CI 0.26-0.87).
  
  
  CONCLUSIONS
  Our study provides new insights into the interplay of anti-/pro-inflammatory cytokines with platelet hyper-reactivity in high-risk patients.
authors.affiliation: Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy. annamaria.gori@unifi.it
authors.forename: A M
authors.initials: AM
authors.lastname: Gori
authors.forename: F
authors.initials: F
authors.lastname: Cesari
authors.forename: R
authors.initials: R
authors.lastname: Marcucci
authors.forename: B
authors.initials: B
authors.lastname: Giusti
authors.forename: R
authors.initials: R
authors.lastname: Paniccia
authors.forename: E
authors.initials: E
authors.lastname: Antonucci
authors.forename: G F
authors.initials: GF
authors.lastname: Gensini
authors.forename: R
authors.initials: R
authors.lastname: Abbate
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000175:diagnosis*; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D017202:Myocardial Ischemia / Q000175:diagnosis; D015539:Platelet Activation; D010974:Platelet Aggregation; D010979:Platelet Function Tests
chemical_list: D016207:Cytokines; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma