Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation

Stacy Robertson, Gonzalo J. Martínez, Cloe A. Payet, Jennifer Y. Barraclough, David S. Celermajer, Christina Bursill, Sanjay Patel

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34 Citations (Scopus)

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.

LanguageEnglish
Pages1237-1246
Number of pages10
JournalClinical Science
Volume130
Issue number14
DOIs
Publication statusPublished - 1 Jan 2016
Externally publishedYes

Keywords

  • Acute coronary syndromes
  • Atherosclerosis
  • Colchicine
  • Inflammasome
  • Monocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Robertson, S., Martínez, G. J., Payet, C. A., Barraclough, J. Y., Celermajer, D. S., Bursill, C., & Patel, S. (2016). Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation. Clinical Science, 130(14), 1237-1246. https://doi.org/10.1042/CS20160090