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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Review Article

Interleukin-6 Signaling in Atherosclerosis: From Molecular Mechanisms To Clinical Outcomes

Author(s): Charalampos Papastamos, Alexios S. Antonopoulos*, Spyridon Simantiris, Nikolaos Koumallos, Marios Sagris, Panagiotis Theofilis, Evangelos Oikonomou, Gerasimos Siasos, Konstantinos Tsioufis and Dimitris Tousoulis

Volume 23, Issue 22, 2023

Published on: 10 August, 2023

Page: [2172 - 2183] Pages: 12

DOI: 10.2174/1568026623666230718141235

Price: $65

Abstract

Interleukin-6 (IL-6) is a cytokine centrally involved in several immune responses and it has been recognized as a driver of enhanced atherothrombotic risk. Immunity and inflammation are intrinsically involved in atherosclerosis progression. This generated ‘inflammation hypothesis’, which is now validated in large-scale clinical trials. Abundant evidence supports the distinctive role of IL-6 in coronary artery disease. The focus on this cytokine stems from epidemiological studies linking high plasma concentrations of IL-6 with greater risk for adverse cardiovascular events, genetic studies which implicate a causative role of IL-6 in atherosclerosis and murine data which support the involvement of IL-6 in various pathophysiological cascades of atherothrombosis. The fact that high IL-6 levels are equivalent to increased cardiovascular risk created an unmet need to address those who are at ‘residual inflammatory risk’. Moreover, the opposing effects of IL-6 underlined the importance of deciphering specific signaling cascades, which may be responsible for different effects. Finally, murine data and some small clinical trials highlighted the possibility of reversing the pro-atherogenic effects of IL-6 by directly targeting it. While IL-1 blockage was proved effective, it is reasonable to examine if moving more downstream in the inflammation cascade could be more selective and effective than other anti-inflammatory therapies. In the present review, we examine the role of IL-6 as a biomarker of ‘residual inflammatory risk’, its vital role in the pathophysiology of atherosclerosis progression and the possibility of targeting it to stall coronary artery disease progression.

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