Interleukin-6 signaling in atherosclerosis: from molecular mechanisms to clinical outcomes

Curr Top Med Chem. 2023 Jul 18. doi: 10.2174/1568026623666230718141235. Online ahead of print.ABSTRACTInterleukin-6 (IL-6) is a cytokine centrally involved in several immunological processes and 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 the 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 the individual 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 proved effective, it is reasonable to examine if moving more downstream in the inflammation cascade could be more selective...
Source: Current Topics in Medicinal Chemistry - Category: Chemistry Authors: Source Type: research