Pulmonary endothelium as a site of synthesis and storage of interleukin-6 in experimental congestive heart failure.
BACKGROUND
Pulmonary endothelium is an early upstream hemodynamic target of left ventricular dysfunction. Interleukin 6 (IL-6) is a pro-inflammatory cytokine reported to increase in congestive heart failure (CHF) patients.


OBJECTIVE
We sought to determine the origin of IL-6, IL-6 receptor (IL-6R) and gp130 in experimental CHF.


METHODS
We used rats with coronary artery ligation as an experimental model of either compensated or decompensated heart failure. Lung and aorta samples were analysed by RT-PCR, ELISA and immunohistochemistry for IL-6 and its receptors.


RESULTS
IL-6 mRNA expression increased in the lung of rats with decompensated heart failure and was positively correlated with infarct severity whereas IL-6R mRNA decreased in the lung of myocardial infarction rats and gp130 mRNA remained unchanged. In contrast, there were no changes in IL-6 mRNA expression in the aorta and left ventricular myocardium. IL-6 peptide content as determined by ELISA and Western Blot in lung tissue was 2-fold higher in decompensated heart failure as compared to control rats. These data were confirmed by immunohistochemistry showing a preferential endothelial localization of IL-6 in the CHF lung. IL-6 peptide was also present in the pleural effusion of decompensated heart failure and was positively correlated with IL-6 mRNA expression in the lungs of decompensated HF rats. Pulmonary IL-6 overexpression was associated with nuclear translocation of NF-kappaB and cytosolic degradation of IkappaB.


CONCLUSIONS
Dysfunctional pulmonary endothelium is a source of synthesis and storage of IL-6 in an experimental model of CHF.
Gaertner
Roger
R
INSERM U460, Cardiovascular Remodelling, CHU Xavier-Bichat, 16 rue Henri Huchard, 75018, Paris, France.
Lepailleur-Enouf
Delphine
D
Gonzalez
Walter
W
Nicoletti
Antonino
A
Mandet
Chantal
C
Philippe
Monique
M
Mercadier
Jean Jacques
JJ
Michel
Jean Baptiste
JB
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015153:Blotting, Western; D050822:Cytokine Receptor gp130; D015536:Down-Regulation / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000503:physiopathology*
D015703:Antigens, CD; C494199:IL6ST protein, human; C494201:Il6st protein, rat; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D050822:Cytokine Receptor gp130