TY - JOUR T1 - Supplemental N-acetylcysteine and other measures that boost intracellular glutathione can downregulate interleukin-1β signalling: a potential strategy for preventing cardiovascular events? JF - Open Heart JO - Open Heart DO - 10.1136/openhrt-2017-000599 VL - 4 IS - 2 SP - e000599 AU - James J DiNicolantonio AU - James H O’Keefe AU - Mark F McCarty Y1 - 2017/07/01 UR - http://openheart.bmj.com/content/4/2/e000599.abstract N2 - A proinflammatory milieu associated with elevations of C-reactive protein (CRP) and homocysteine has been linked epidemiologically to increased risk for myocardial infarction (MI). Nonetheless, there is good reason to suspect that neither CRP nor homocysteine are mediators of this risk, but rather serve as markers for increased activity of another agent or agents that are true mediators.1–4 The search for such a mediator has cast suspicion on interleukin (IL)-1β, which, in conjunction with IL-6, boosts hepatic expression of CRP.5 6 While the effects of IL-1β on hepatic acute phase protein expression are variable, IL-1β also promotes hepatic synthesis of serum amyloid A, another acute phase reactant linked to increased cardiovascular (CV) risk.5 7 Furthermore, there is some reason to suspect that IL-1β may act on the liver to boost homocysteine levels.8 Rodent and cell culture studies indicate that IL-1β can promote atherogenesis by via effects on endothelial, smooth muscle and foam cells.9–16 Conversely, apolipoprotein E knockout mice in which IL-1β has likewise been knocked out, or that are treated with a monoclonal antibody targeting IL-1β, are less prone to atherogenesis.17–-19 The impact of canakinumab, a monoclonal antibody targeting IL-1β, is now being studied for secondary prevention of MI in patients with elevated CRP in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) multicenter trial.20 This trial should provide important insight regarding the suspected role of IL-1β in coronary events. A pilot study has already confirmed that canakinumab can markedly lower elevated CRP; its impact on homocysteine has not yet been evaluated.21 The ability of potent statin therapy to decrease risk for coronary events in patients with elevated CRP but low-normal low density lipoprotein (LDL) cholesterol might reflect a suppressive impact of statins on IL-1β activation via inflammasomes.22–25 While canakinumab may prove to be an important therapeutic asset … ER -