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

Clin Sci (Lond). 2016 Jul 1;130(14):1237-46. doi: 10.1042/CS20160090. Epub 2016 Apr 21.


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.

Keywords: acute coronary syndromes; atherosclerosis; colchicine; inflammasome; monocytes.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / immunology
  • Acute Coronary Syndrome / metabolism
  • Aged
  • Aged, 80 and over
  • Caspase 1 / metabolism*
  • Cells, Cultured
  • Colchicine / pharmacology
  • Colchicine / therapeutic use*
  • Female
  • Humans
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Male
  • Middle Aged
  • Monocytes / drug effects*
  • Monocytes / physiology
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors*


  • Interleukin-18
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Caspase 1
  • Colchicine