title: CXC-chemokines, a new group of cytokines in congestive heart failure--possible role of platelets and monocytes.
abstract: OBJECTIVE
  The purpose of the present study was to examine the circulating levels of CXC-chemokines in patients with various degree of congestive heart failure (CHF).
  
  
  BACKGROUND
  CXC-chemokines may be important mediators in the persistent immune activation observed in CHF patients by activation of circulating neutrophils, T-cells and monocytes and possibly by the recruitment of these cells into the failing myocardium.
  
  
  METHODS
  Levels of interleukin (IL)-8, growth-regulated oncogene (GRO) alpha and epithelial neutrophil activating peptide (ENA)-78 were measured both in serum and in platelet-free plasma by enzyme immunoassay in 47 patients with CHF and in 20 healthy controls.
  
  
  RESULTS
  (i) CHF patients had significantly elevated levels of all the three CXC-chemokines with IL-8 and GRO alpha showing a gradual increase along with increasing NYHA class. (ii) There was an inverse correlation between IL-8 and left ventricular ejection fraction (EF) and cardiac index (CI). (iii) Both unstimulated and lipopolysaccharide (LPS)-stimulated monocytes from CHF patients released markedly elevated amounts of all three CXC-chemokines. (iv) Platelets from patients with severe CHF were characterised by decreased content of GRO alpha and ENA-78 as well as decreased release of these chemokines upon thrombin receptor stimulation. (v) Activated platelets stimulated peripheral blood mononuclear cells in vitro to enhanced release of IL-8, and neutralising antibodies against ENA-78 inhibited this interaction.
  
  
  CONCLUSIONS
  This study demonstrates for the first time elevated levels of CXC-chemokines in CHF, which may be of importance for progression of heart failure. Our findings further suggest that activated monocytes and platelets may contribute to enhanced CXC-chemokine levels in CHF.
authors.affiliation: Department of Cardiology, University of Oslo, National Hospital, Norway.
authors.forename: J K
authors.initials: JK
authors.lastname: Damås
authors.forename: L
authors.initials: L
authors.lastname: Gullestad
authors.forename: T
authors.initials: T
authors.lastname: Ueland
authors.forename: N O
authors.initials: NO
authors.lastname: Solum
authors.forename: S
authors.initials: S
authors.lastname: Simonsen
authors.forename: S S
authors.initials: SS
authors.lastname: Frøland
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D000704:Analysis of Variance; D016022:Case-Control Studies; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D019743:Chemokines, CXC / Q000097:blood*; D002630:Chemotactic Factors / Q000097:blood; D005260:Female; D006133:Growth Substances / Q000097:blood; D006333:Heart Failure / Q000097:blood* / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000031:analogs & derivatives / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D018709:Statistics, Nonparametric
chemical_list: C475829:CXCL1 protein, human; C486263:CXCL5 protein, human; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8