© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
CXC-chemokines, a new group of cytokines in congestive heart failure — possible role of platelets and monocytes
aDepartment of Cardiology, University of Oslo The National Hospital, N-0027 Oslo, Norway
bResearch Institute for Internal Medicine, University of Oslo The National Hospital, N-0027 Oslo, Norway
cSection of Endocrinology, University of Oslo The National Hospital, N-0027 Oslo, Norway
dSection of Clinical Immunology and Infectious Diseases, Department of Internal Medicine, University of Oslo The National Hospital, N-0027 Oslo, Norway
* Corresponding author. Tel.: +47-22-86-7010; Fax: +47-22-86-8242 pal.aukrust{at}klinmed.uio.no
Objectives: 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)
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 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 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.
KEYWORDS Cytokines; Heart failure; Infection/inflammation; Leukocytes; Platelets
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