New data indicate that one pattern of IL-1 genetic polymorphisms, characterized by the IL-1A (+4845) and IL-1B (+3954) markers, is associated with periodontitis but not certain measures of atherosclerosis.
Moreover, the transcripts of interleukin 1 beta (IL-1β) and tumor necrosis factor α (TNFα), which are related to atherosclerosis, were up-regulated by TCDD stimulation.
Thus, in monocytes/macrophages, LPS, NEU1 and IL-1β act in a positive feedback loop as enhancers of inflammation and may therefore promote atherosclerosis and plaque instability.
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).
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.
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.
Taken together, these results show that IL-1β has multiple beneficial effects in late-stage murine atherosclerosis, including promotion of outward remodeling and formation and maintenance of an SMC- and collagen-rich fibrous cap.
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.
Interleukin-1β (IL-1β), a prototypic multifunctional cytokine involved in inflammation, has an important effect on the pathogenesis and progression of atherosclerosis.
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.
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]).
Although the mechanisms had been unclear, emerging evidence unveiled that NLRP3 inflammasomes, which regulate caspase-1 activation and subsequent processing of pro-IL-1β, trigger vascular wall inflammatory responses and lead to progression of atherosclerosis.
<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.
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.
The association between the IL-1 system and atherosclerosis is complex and may vary as a result of a number of factors, such as stage of disease, clinical phenotype, and possibly population characteristics.
IL-1 was implicated as a cardiodepressant factor in septic shock, and subsequent pre-clinical and clinical research has defined important roles for IL-1 in atherosclerosis, acute myocardial infarction (AMI), and heart failure (HF).
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.
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.
Secretion of the cytokine interleukin-1β (IL-1β) by macrophages, a major driver of pathogenesis in atherosclerosis, requires two steps: Priming signals promote transcription of immature IL-1β, and then endogenous "danger" signals activate innate immune signaling complexes called inflammasomes to process IL-1β for secretion.
Diacerein may have therapeutic applications to diminish IL-1-induced skin inflammation in psoriasis and attenuate IL-1-induced development of atherosclerosis.