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

Curr Top Med Chem. 2023;23(22):2172-2183. doi: 10.2174/1568026623666230718141235.

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.

Keywords: Atherosclerosis; Atherothrombotic risk; Coronary artery disease; Inflammation cascade; Interleukin-6; Residual inflammatory risk.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis* / drug therapy
  • Coronary Artery Disease* / drug therapy
  • Cytokines
  • Humans
  • Inflammation / drug therapy
  • Interleukin-6
  • Mice

Substances

  • Interleukin-6
  • Cytokines