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Interleukin-1 blockade in cardiovascular diseases: a clinical update

Interleukin-1 blockade in cardiovascular diseases: a clinical update Interleukin-1 (IL-1) is the prototypical pro-inflammatory cytokine. IL-1 was implicated as a cardiodepressant factor in septic shock, and subsequent pre-clinical and clinical research has defined important roles for IL-1 in atherosclerosis, acute myocardial infarction (AMI), and heart failure (HF). IL-1 promotes the formation of the atherosclerotic plaque and facilitates its progression and complication. In a large phase III clinical trial of stable patients with prior AMI, blocking IL-1 activity using a monoclonal antibody prevented recurrent atherothrombotic cardiovascular events. IL-1 also contributes to adverse remodelling and left ventricular dysfunction after AMI, and in phase II studies, IL-1 blockade quenched the inflammatory response associated with ST-segment elevation AMI and prevented HF. In patients with established HF, IL-1 is thought to impair beta-adrenergic receptor signalling and intracellular calcium handling. Phase II studies in patients with HF show improved exercise capacity with IL-1 blockade. Thus, IL-1 blockade is poised to enter the clinical arena as an additional strategy to reduce the residual cardiovascular risk and/or address inflammatory cardiovascular conditions refractory to standard treatments. There are several IL-1 blockers available for clinical use, which differ in mechanism of action, and potentially also efficacy and safety. While IL-1 blockade is not immunosuppressive and not associated with opportunistic infections or an increased risk of cancer, fatal infections may occur more frequently while on treatment with IL-1 blockers likely due to a blunting of the inflammatory signs of infection leading to delayed presentation and diagnosis. We discuss the practical use of IL-1 blockade, including considerations for patient selection and safety monitoring. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal Oxford University Press

Interleukin-1 blockade in cardiovascular diseases: a clinical update

Buckley, Leo F; Abbate, Antonio
European Heart Journal , Volume 39 (22): 7 – Mar 23, 2018
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Publisher
Oxford University Press
Copyright
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.
ISSN
0195-668X
eISSN
1522-9645
DOI
10.1093/eurheartj/ehy128
Publisher site
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Abstract

Interleukin-1 (IL-1) is the prototypical pro-inflammatory cytokine. IL-1 was implicated as a cardiodepressant factor in septic shock, and subsequent pre-clinical and clinical research has defined important roles for IL-1 in atherosclerosis, acute myocardial infarction (AMI), and heart failure (HF). IL-1 promotes the formation of the atherosclerotic plaque and facilitates its progression and complication. In a large phase III clinical trial of stable patients with prior AMI, blocking IL-1 activity using a monoclonal antibody prevented recurrent atherothrombotic cardiovascular events. IL-1 also contributes to adverse remodelling and left ventricular dysfunction after AMI, and in phase II studies, IL-1 blockade quenched the inflammatory response associated with ST-segment elevation AMI and prevented HF. In patients with established HF, IL-1 is thought to impair beta-adrenergic receptor signalling and intracellular calcium handling. Phase II studies in patients with HF show improved exercise capacity with IL-1 blockade. Thus, IL-1 blockade is poised to enter the clinical arena as an additional strategy to reduce the residual cardiovascular risk and/or address inflammatory cardiovascular conditions refractory to standard treatments. There are several IL-1 blockers available for clinical use, which differ in mechanism of action, and potentially also efficacy and safety. While IL-1 blockade is not immunosuppressive and not associated with opportunistic infections or an increased risk of cancer, fatal infections may occur more frequently while on treatment with IL-1 blockers likely due to a blunting of the inflammatory signs of infection leading to delayed presentation and diagnosis. We discuss the practical use of IL-1 blockade, including considerations for patient selection and safety monitoring.

Journal

European Heart Journal – Oxford University Press

Published: Mar 23, 2018

Keywords: Interleukin-1; Inflammation; Coronary artery disease; Heart failure

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