Robertson, S., Martínez, G. J., Payet, C. A., Barraclough, J. Y., Celermajer, D. S., Bursill, C. and Patel, S. (2016) Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation. Clinical Science, 130(14), pp. 1237-1246. (doi: 10.1042/CS20160090) (PMID:27129183)
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Abstract
Inflammasome activation, with subsequent release of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, has recently been implicated in atherosclerosis-associated inflammation. This study aims to assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. ACS patients (n=21) were randomized to oral colchicine (1 mg followed by 0.5 mg 1 h later) or no treatment, and compared with untreated healthy controls (n=9). Peripheral venous blood was sampled pre- (day 1) and 24 h post- (day 2) treatment. Monocytes were cultured and stimulated with ATP. Analysis of key inflammasome markers was performed by ELISA. IL-1β secretion increased by 580.4% (P<0.01) in ACS patients compared with controls but only with ATP stimulation. Untreated ACS patients secreted significantly higher levels of IL-18 compared with healthy controls independent of ATP stimulation (P<0.05). Colchicine treatment in ACS patients markedly reduced intracellular and secreted levels of IL-1β compared with pre-treatment levels (P<0.05 for both), as well as significantly reducing pro-caspase-1 mRNA levels by 57.7% and secreted caspase-1 protein levels by 30.2% compared with untreated patients (P<0.05 for both). Monocytes from ACS patients are ‘primed’ to secrete inflammasome-related cytokines and short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1β.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Robertson, Dr Stacy |
Authors: | Robertson, S., Martínez, G. J., Payet, C. A., Barraclough, J. Y., Celermajer, D. S., Bursill, C., and Patel, S. |
Subjects: | Q Science > QP Physiology |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | Clinical Science |
Publisher: | Portland Press |
ISSN: | 0143-5221 |
ISSN (Online): | 1470-8736 |
Published Online: | 13 June 2016 |
Copyright Holders: | Copyright © 2016 The Authors |
First Published: | First published in Clinical Science 130(14): 1237-1246 |
Publisher Policy: | Reproduced in accordance with the publisher copyright policy |
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