CXC-chemokines, a new group of cytokines in congestive heart failure--possible role of platelets and monocytes.
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.
Damås
J K
JK
Department of Cardiology, University of Oslo, National Hospital, Norway.
Gullestad
L
L
Ueland
T
T
Solum
N O
NO
Simonsen
S
S
Frøland
S S
SS
Aukrust
P
P
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
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