Interleukin-1 Beta as a Target for Atherosclerosis Therapy

Abstract

Inflammatory pathways drive atherogenesis and link traditional risk factors to atherosclerosis and its complications. One inflammatory mediator has come to the fore as a therapeutic target in cardiovascular disease. The experimental and clinical evidence reviewed here support interleukin-1 beta (IL-1β) as both a local vascular and systemic contributor in this regard. Intrinsic vascular wall cells and lesional leukocytes alike can produce this cytokine. Local stimuli in the plaque favor the generation of active IL-1β through the action of a molecular assembly known as the inflammasome. Clinically applicable interventions that interfere with IL-1 action can improve cardiovascular outcomes, ushering in a new era of anti-inflammatory therapies for atherosclerosis. The translational path described here illustrates how advances in basic vascular biology may transform therapy. Biomarker-directed application of anti-inflammatory interventions promises to help us achieve a more precise and personalized allocation of therapy for our cardiovascular patients.

Associations of ideal cardiovascular health with GlycA, a novel inflammatory marker: The Multi‐Ethnic Study of Atherosclerosis

“…GlycA is derived from glycosylation of five major acute phase inflammatory proteins and may be a more stable marker of systemic inflammation than some of the other traditional markers . Targeting inflammation has become increasingly recognized as an important CVD prevention strategy . Findings from the recent Canakinumab Anti‐inflammatory Thrombosis Outcome Study (CANTOS) further highlight that reductions in CVD, independent of lipids, can be made by targeting systemic inflammation .…”

“…Inflammation plays a key role in the pathogenesis of cardiovascular disease (CVD), and recently inflammation has become a direct target of therapy for CVD prevention . High‐sensitivity C‐reactive protein (hsCRP), a marker of systemic inflammation, has been shown to be associated with incident CVD events .…”

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

“…New compounds that interfere with IL-1 and IL-6 signalling are under investigation 163,167 . The CANTOS trial 168 has revealed that anti-inflammatory therapy with canakinumab, a human monoclonal anti-IL-1β antibody, significantly reduced recurrent cardiovascular events in >10,000 stable patients who had residual inflammation after myocardial infarction, independent of lowered lipid levels 169 .…”

The Canakinumab Antiinflammatory Thrombosis Outcome Study trial—the starting gun has fired

“…The IL-1ra approach has had a modest benefit in overt inflammatory conditions such as rheumatoid arthritis (3) and a significant effect in anti-inflammatory conditions characterised by over activity of the inflammasome (4). The IL-1 pathway has considerable preclinical data to support its involvement in atherogenesis, the inflammatory response to fat feeding and the response to vessel wall response to injury (5)(6)(7). Whilst these studies, conducted as they were in laboratory animals have all been consistent with a hypothesis that IL-1 is atherogenic, human genetic studies…”