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.
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.
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.
These results demonstrate for the first time that an antibody targeting IL-1β can inhibit the progression of atherosclerosis in vivo, highlighting the importance of this key cytokine in cardiovascular disease.
By augmenting macrophage TFEB, the master transcriptional regulator of autophagy-lysosomal biogenesis, we can reverse the autophagy dysfunction of plaques, enhance aggrephagy of p62-enriched protein aggregates and blunt macrophage apoptosis and pro-inflammatory IL-1β levels, leading to reduced 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.
We show that IL-33, which is a novel IL-1-like cytokine that signals via ST2, can reduce atherosclerosis development in ApoE(-/-) mice on a high-fat diet.
However, upstream inhibition of CC-induced inflammation by using a complement inhibitor may be more efficient in treating atherosclerosis since this will block initiation of inflammation processes before downstream release of cytokines including IL-1β.
IL-1 (interleukin 1) has an established role in atherosclerosis and inflammation, although whether IL-1 inhibition modulates blood pressure is unclear.
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.
The IL-1β-induced inflammation-activated endothelial cell (EC)-smooth muscle cell (SMC)-mononuclear cell (MC) co-culture model was established, based on the changes in a series of atherosclerosis-associated inflammatory markers secreted by ECs and SMCs.
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.
Validation by real-time polymerase chain reaction was undertaken with 2 genes known to be up-regulated in atherosclerosis (interleukin 1beta [IL-1beta] and IL-8) and 2 novel genes identified by the array analysis (signal transducer and activator of transcription 6 [STAT6] and IL-1 receptor-associated kinase [IRAK]).
Moreover, miR-144-3p mimics (agomir) enhanced the expression of inflammatory factors, including IL-1β, IL-6 and TNF-α, in vivo and in vitro, inhibited cholesterol efflux in THP-1 macrophage-derived foam cells, decreased HDL-C circulation and impaired RCT in vivo, resulting in accelerated pathological progression of atherosclerosis in apoE-/- mice.
The successful results of a recent randomized controlled clinical trial targeting inflammasome with anti-IL1β monoclonal antibody in non-autoimmune conditions, prove that specific immunotherapy can be a promising and effective strategy to control atherosclerosis in rheumatic diseases as well.
Here, we review the mechanisms of NLRP3 inflammasome activation and proinflammatory IL-1 family cytokine production in the context of atherosclerosis and discuss treatment possibilities in light of the positive outcomes of the CANTOS trial.
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.
However, dysregulated release of IL-1β can be detrimental and is attributed to the progression and pathogenesis of multiple inflammatory diseases including, rhuematoid arthritis (RA), atherosclerosis, type 2 diabetes (T2D), Alzheimers disease and gout.IL-1β is encoded as a pro-protein.
These data also suggest that inhibition of this potentially important source of chronic inflammation in atherosclerosis requires blockade of interleukin-1α and not interleukin-1β.