Using the multivariate analysis, a significant association between TNF-α and IL- 1( levels, and a higher chance of atherosclerosis development in HIV group were observed.
Ligands of this family such as TNFα, CD40L, and IL-1β promote chronic inflammatory processes such as atherosclerosis and restenosis, the latter being a common adverse reaction after vascular interventions.
Cytokines involved in human atherosclerosis can be broadly classified as proinflammatory and proatherogenic (such as IL-1, IL-6, and TNF [tumor necrosis factor]) or as anti-inflammatory and antiatherogenic (such as IL-10 and IL-1rA).
Excessive IL-1β production is a characteristic of most chronic inflammatory diseases, including atherosclerosis, type 2 diabetes, and obesity, which affect a large proportion of the global population.
IL-1β induces SAA1 expression in HCAEC and promotes its intercellular exchange, suggesting that direct communication between cells in inflammatory conditions could ultimately lead to faster development of atherosclerosis in coronary arteries.
We first observe that high-salt intake promotes atherosclerosis formation in the aortas of ApoE<sup>-/-</sup> mice, through inducing the expression of NFAT5, NLRP3, and IL-1β in endothelium.
Patients with rheumatic diseases have an increased risk of atherosclerosis with up-regulated serum amyloid A (SAA), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), which were reported to activate human coronary artery endothelial cells (HCAEC).
Furthermore, oral administration of NATOH down-regulated NF-κB-dependent expression of pro-inflammatory markers (including IL-1β and adhesion molecules) and ameliorated atherosclerosis in Apo E knockout mice.
Here we summarize the current state of knowledge regarding the pro-inflammatory and disease-modulating role of the IL-1 family in atherosclerosis, myocardial infarction, aneurysm, stroke, and other CVDs.
Targeted inhibition of interleukin 1β with canakinumab provided the proof of principle that limiting inflammation can improve outcomes in atherosclerotic vascular disease, but long-term treatment with a monoclonal antibody is unlikely to have widespread uptake.
<b>Results:</b> Our results indicated that the protein levels of HMGB1, TLR4, and pro-inflammatory cytokines including IL-1β, TNF-α were elevated with the development of atherosclerosis in CUMS mice, while the expressions of PPARγ, LXRα, and ABCA1 declined.
The levels of blood lipids, atherosclerotic plaques (AP) formation, the lipid content, collagen content, apoptosis of aortic cells, angiogenesis as well as the expression of inflammatory factors, such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were determined through a series of experiments.MIAT was found to be upregulated in AS.
Compared with control mice, increased plasma lipids and proinflammatory interleukin-1β, aggravated macrophage infiltration into the atherosclerotic lesion, and accelerated development of atherosclerosis were observed in diabetic mice, which were associated with the activation of NLRP3 inflammasomes and dysregulation of thioredoxin-1 and thioredoxin-interacting protein.
Yet, some mouse data have shown a prominent role of IL-1α rather than IL-1β in atherosclerosis, or even a deleterious effect of IL-1 on outward arterial remodelling in atherosclerosis-susceptible mice.
In the recently concluded Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial, investigators looked at the potential role of IL-1 (especially IL-1β) inhibition in halting the progression of atherosclerosis.
IL-1β inhibition with canakinumab reduces major adverse cardiovascular event rates among high-risk atherosclerosis patients with CKD, particularly among those with a robust anti-inflammatory response to initial treatment.
This study is that ginsenoside Rb1 exerted an inhibitory effect on early atherosclerosis in ApoE-/- mice via decreasing body weight and food intake daily, upregulating the lipid levels of serum plasma, including those of TC, TG and LDL-C and HDL-C and reducing the atherosclerotic plaque area, suppressing inflammatory cytokines (levels of IL-1β, IL-6 and TNF-α) in the serum of ApoE-/- mice, changing the expression levels of BCL-2, BAX, cleaved caspase-3 and cleaved caspase-9 and weakening apoptosis associated with anti-inflammatory activity.
Targeting the IL-1β pathway has already been successful with canakinumab but its expense and inconvenience of administration may limit its widespread uptake for controlling inflammation in atherosclerosis.
It is now also known that cholesterol crystals are present through all stages of atherosclerosis and can activate the NLRP3 inflammasome within these inflammatory cells to produce interleukin 1β and interleukin 18 - key mediators in the inflammatory cascade that drive plaque progression and instability.
IL-1 (interleukin 1) has an established role in atherosclerosis and inflammation, although whether IL-1 inhibition modulates blood pressure is unclear.
CCAAT/enhancer binding proteins β (C/EBPβ), a regulator of IL-1β production, recently been evidenced as a key player in the development of atherosclerosis.