Cytokines release inhibition from activated monocytes, and reduction of in-stent neointimal growth in humans.
OBJECTIVE
Atherosclerosis and restenosis are largely ruled by inflammation. The aim of this study was to test the effects of a short-course, high-dose oral prednisone on the release of interleukin-6 (IL-6) and tumour necrosis factor (TNF)-alpha from circulating monocytes and on the neointimal growth that follows bare metal stent (BMS) implantation. In a sub-group of patients activated NF-kappaB was also evaluated.


METHODS
Out of 40 patients with coronary artery disease treated with BMS implantation, 20 were randomly assigned to receive oral prednisone during 40 days according to a standardized protocol. In non-stimulated and stimulated (LPS and PMA) monocytes we evaluated the release of IL-6 and TNF-alpha, and NF-kappaB p50 subunit translocation at baseline, at 10 and 30 days. Late luminal loss (LLL) 9 months after angioplasty was calculated by quantitative coronary angiography.


RESULTS
Plasma concentrations of prednisone correlated inversely with IL-6 and TNF-alpha release (R2=0.45, p=0.04 and R2=0.69, p=0.005, respectively) and NF-kappaB activation from monocytes (R2=0.58, p=0.01). The reduction of TNF-alpha release and NF-kappaB activation were significantly related (R2=0.56, p=0.01). Prednisone patients showed a significantly larger reduction of cytokine release and NF-kappaB activation compared to non-treated patients, at 10 days and 30 days. LLL was lower in the prednisone group (0.44+/-0.35 mm versus 0.80+/-0.53 mm, p=0.02) and correlated with reduction of TNF-alpha (R2=0.41, p=0.01).


CONCLUSIONS
High doses of oral prednisone reduce NF-kappaB pathway activation and pro-inflammatory cytokine release in circulating activated monocytes of patients treated with coronary stenting. TNF-alpha release reduction correlates with decreased LLL.
Pesarini
Gabriele
G
Department of Biomedical Sciences and Surgery, University of Verona, Division of Cardiology, and Laboratory of Clinical Biochemistry and Haematology of the Ospedale Civile Maggiore, Verona, Italy.
Amoruso
Angela
A
Ferrero
Valeria
V
Bardelli
Claudio
C
Fresu
Luigia Grazia
LG
Perobelli
Laura
L
Scappini
Paolo
P
De Luca
Giuseppe
G
Brunelleschi
Sandra
S
Vassanelli
Corrado
C
Ribichini
Flavio
F
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000601:surgery; D023903:Coronary Restenosis / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism*; D011241:Prednisone / Q000627:therapeutic use*; D015607:Stents; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D011241:Prednisone