Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation.
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.
['Robertson|Stacy|S|', 'Martínez|Gonzalo J|GJ|', 'Payet|Cloe A|CA|', 'Barraclough|Jennifer Y|JY|', 'Celermajer|David S|DS|', 'Bursill|Christina|C|', 'Patel|Sanjay|S|']
D054058:Acute Coronary Syndrome D000368:Aged D000369:Aged, 80 and over D020170:Caspase 1 D002478:Cells, Cultured D003078:Colchicine D005260:Female D006801:Humans D020382:Interleukin-18 D053583:Interleukin-1beta D008297:Male D008875:Middle Aged D009000:Monocytes D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
colchicine acute coronary syndromes inflammasome monocytes atherosclerosis