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

• DOI: 10.1042/cs20160090
• Publication Date: 2016-04-22T02:24:37Z
• Authors: Stacy Robertson; Gonzalo J. Martínez; Cloe A. Payet; Jennifer Y. Barra...; David S. Celermajer; Christina Bursill; Sanjay Patel
• Keywords: Colchicine; Monocyte

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 acute coronary syndrome (ACS) patients (1) inflammasome activation circulating monocytes (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that shown be cardio-protective clinical studies, might acutely suppress inflammasome-dependent ACS (n=21) were randomized colchicine (1 mg followed by 0.5 1 h later) or no treatment, compared untreated healthy controls (n=9). Peripheral venous blood was sampled pre- (day 1) 24 post- 2) treatment. Monocytes cultured stimulated ATP. Analysis key markers performed ELISA. IL-1β secretion increased 580.4% (P<0.01) but only ATP stimulation. Untreated secreted significantly higher levels IL-18 independent stimulation (P<0.05). Colchicine treatment markedly reduced intracellular pre-treatment (P<0.05 for both), as well reducing pro-caspase-1 mRNA 57.7% caspase-1 protein 30.2% both). from are ‘primed’ secrete inflammasome-related suppresses monocyte activity, thereby IL-1β.