Cytokines release inhibition from activated monocytes, and reduction of in-stent neointimal growth in humans

Pesarini, Gabriele; Amoruso, Angela; Ferrero, Valeria; Bardelli, Claudio; Fresu, Luigia Grazia; Perobelli, Laura; Scappini, Paolo; De Luca, Giuseppe; Brunelleschi, Sandra; Vassanelli, Corrado; Ribichini, Flavio

doi:10.1016/j.atherosclerosis.2010.02.004

« Previous Next »Atherosclerosis
Volume 211, Issue 1 , Pages 242-248, July 2010

Cytokines release inhibition from activated monocytes, and reduction of in-stent neointimal growth in humans

Gabriele Pesarini
- Department of Biomedical Sciences and Surgery, University of Verona, Division of Cardiology, Verona, Italy
Angela Amoruso
- Department of Medical Sciences, University of Piemonte Orientale “A. Avogadro”, Novara, Italy
Valeria Ferrero
- Department of Biomedical Sciences and Surgery, University of Verona, Division of Cardiology, Verona, Italy
Claudio Bardelli
- Department of Medical Sciences, University of Piemonte Orientale “A. Avogadro”, Novara, Italy
Luigia Grazia Fresu
- Department of Medical Sciences, University of Piemonte Orientale “A. Avogadro”, Novara, Italy
Laura Perobelli
- Laboratory of Clinical Biochemistry and Haematology of the Ospedale Civile Maggiore, Verona, Italy
Paolo Scappini
- Laboratory of Clinical Biochemistry and Haematology of the Ospedale Civile Maggiore, Verona, Italy
Giuseppe De Luca
- Department of Medical Sciences, University of Piemonte Orientale “A. Avogadro”, Novara, Italy
Sandra Brunelleschi
- Department of Medical Sciences, University of Piemonte Orientale “A. Avogadro”, Novara, Italy
Corrado Vassanelli
- Department of Biomedical Sciences and Surgery, University of Verona, Division of Cardiology, Verona, Italy
Flavio Ribichini
- Department of Biomedical Sciences and Surgery, University of Verona, Division of Cardiology, Verona, Italy
- Corresponding author at: Catheterization Laboratory of the University of Verona, Ospedale Civile Maggiore, Piazzale A. Stefani 1, 37126, Verona, Italy. Tel.: +39 045 812 2039; fax: +39 045 802 7307.

Received 14 June 2009; received in revised form 19 January 2010; accepted 1 February 2010. published online 08 March 2010.

Abstract

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)-α from circulating monocytes and on the neointimal growth that follows bare metal stent (BMS) implantation. In a sub-group of patients activated NF-κB 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-α, and NF-κB 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-α release (R²=0.45, p=0.04 and R²=0.69, p=0.005, respectively) and NF-κB activation from monocytes (R²=0.58, p=0.01). The reduction of TNF-α release and NF-κB activation were significantly related (R²=0.56, p=0.01). Prednisone patients showed a significantly larger reduction of cytokine release and NF-κB activation compared to non-treated patients, at 10 days and 30 days. LLL was lower in the prednisone group (0.44±0.35mm versus 0.80±0.53mm, p=0.02) and correlated with reduction of TNF-α (R²=0.41, p=0.01).

Conclusions

High doses of oral prednisone reduce NF-κB pathway activation and pro-inflammatory cytokine release in circulating activated monocytes of patients treated with coronary stenting. TNF-α release reduction correlates with decreased LLL.

Keywords: Cytokines, Monocytes, Inflammation, Prednisone, Restenosis