Do Interleukin-1 and Interleukin-6 Antagonists Hold Any Place in the Treatment of Atherosclerotic Cardiovascular Disease and Related Co-Morbidities? An Overview of Available Clinical Evidence

Abstract

Cardiovascular disease (CVD) constitutes a real pandemic of the 21st century. According to data from the Centers for Disease Control and Prevention, one person dies every 34 min due to some form of CVD in the United States. Apart from the extremely high morbidity and mortality accompanying CVD, the economic burden seems to be unbearable even for developed countries in the Western World. The role of inflammation in the development and progression of CVD appears to be crucial, while, various inflammatory pathways, such as the Nod-like receptor protein 3 (NLRP3) inflammasome-interleukin (IL)-1/IL-6 pathway of the innate immunity, have attracted scientific interest during the last decade, as a potential treatment target in primary and/or secondary prevention of CVD. Whereas there is a significant amount of evidence, stemming mainly from observational studies, concerning the cardiovascular safety of IL-1 and IL-6 antagonists in patients with rheumatic diseases, evidence from relevant randomized controlled trials (RCTs) is rather scarce and conflicting, especially for patients without underlying rheumatic disease. In this review, we summarize and critically present the currently available evidence, both from RCTs and observational studies, concerning the place that IL-1 and IL-6 antagonists may hold in the treatment of CVD.

Apolipoprotein B and Interleukin 1 Receptor Antagonist: Reversing the Risk of Coronary Heart Disease

“…On one hand, IL-1RA is known to bind to the IL-1 receptor, thereby preventing the binding of both IL-1α and IL-1β, and it has been proposed that inhibiting the IL-1 pathway may prevent the development of various CVDs, including atherosclerosis, MI, and heart failure. 7,41 On the other hand, it has been indicated that IL-1 can directly affect lipid metabolism by suppressing the activity of lipoprotein lipase. 6 Observational studies revealed a positive and significant correlation between IL-1RA and several molecules related to lipid metabolism, including cholesterol, triglycerides, and apolipoproteins B, all of which are known risk factors for CHD.…”

“…Several drugs targeting IL-1 have been investigated for the treatment of CVDs, including Canakinumab, Rilonacept, and Anakinra (a human recombinant IL1-Ra and a first-line agent for RA). 7 In a randomized controlled trial (RCT) involving 80 patients with RA, Anakinra was found to significantly improve various vascular function indices as well as myocardial deformation and twisting. 8 However, another RCT of 182 patients with non-ST elevation acute coronary syndrome suggested that .…”

Interleukins: Pathogenesis in Non-Alcoholic Fatty Liver Disease

“…The NASH is accompanied by increased expression of pro-inflammatory mediators (e.g., IL-1β and TNF-α). Anakinra, a recombinant sort of IL-1Ra, has demonstrated favorable cardiometabolic effects in type 2 diabetic patients, showing improved hyperglycemia and beta-cell secretory function [ 11 , 12 ]. Studies indicate that signals mediated by bile acid farnesoid X receptor (FXR), including the enterohepatic hormone fibroblast growth factor 15/19, play a role in regulating glucose and TG metabolism in NASH [ 11 ].…”

“…Moreover, the additional hepatic accumulation of TG occurs due to the properties of IL-1α that upregulate de novo lipogenesis genes in hepatocytes. Thus, IL-1α instigates an inflammatory response, i.e., the key feature of NASH progression [ 12 ].…”

The comparison of eight-week high-intensity interval training VS. moderate-intensity continuous training on inflammatory and metabolic biomarkers in type II diabetes: a pilot randomized controlled trial

“…Furthermore, there is some evidence suggesting that calprotectin in urine and blood can indicate detrimental effects of in ammatory pathways, such as vascular damage and renal dysfunction (13). IL-6 as a multifunctional cytokine has been shown to increase the risk of atherosclerosis (14). Chronic in ammation therefore underlies both insulin resistance and atherosclerosis.…”