Most advanced are clinical studies with IL-1 antagonists showing improved β-cell function and glycemia and prevention of cardiovascular diseases and heart failure.
These randomized double-blind placebo-controlled data suggest that therapy with canakinumab, an interleukin-1β inhibitor, is related to a dose-dependent reduction in HHF and the composite of HHF or heart failure-related mortality in a population of patients with prior myocardial infarction and elevations in high-sensitivity C-reactive protein.
Inflammasome activation and IL-1β secretion are implicated in myocardial infarction (MI) and resultant heart failure; however, little is known about how macrophage lysosomes regulate these processes.
Compared with those who took no IL-1 blockage, patients taking IL-1 blockage experienced a decreased risk of overall MACE (RR 0.88, 95% CI 0.82-0.94), unstable angina (RR 0.80, 95% CI 0.66-0.98), and breakthrough or recurrence of heart failure (RR 0.44, 95% CI 0.22-0.87).
These studies demonstrate that circulating IL-1β, which increases in cardiovascular disorders such as hypertension and heart failure, acts on the SFO to increase inflammation and RAS activity in the SFO and PVN and that intervening in these neurochemical processes in the SFO can significantly reduce the sympathetic response.
These data suggest that individuals with TET2-mediated clonal hematopoiesis may be at greater risk of developing heart failure and respond better to IL-1β-NLRP3 inflammasome inhibition.
The purpose of this study was to examine the effects of exercise on changes in ASC methylation and activation of the IL-1 family cytokine IL-1β in persons with HF.
Interestingly, interfering with IL-1 has proved to be also effective in other cardiovascular manifestations, such as myocarditis, arrhythmias, and heart failure.
Immunomodulatory interventions in myocardial infarction and heart failure: a systematic review of clinical trials and meta-analysis of IL-1 inhibition.
The promising results of phase II clinical trials of IL-1 blockade in patients with acute myocardial infarction and heart failure have been followed by a successful phase III trial in patients with prior acute myocardial infarction.
Activation of hypothalamic OXT neurons to elevate parasympathetic tone reduced cellular hypertrophy, levels of IL-1β, and fibrosis during TAC-induced HF in rats.
We hypothesized that administration of IL-1 (interleukin-1) receptor antagonist (anakinra) could inhibit the inflammatory response and improve peak aerobic exercise capacity in patients with recently decompensated systolic HF.
Recombinant human IL-18-binding protein (IL-18BP) or an IL-18-blocking antibody (IL-18AB) was used to neutralize endogenous IL-18 after challenge with the plasma of patients with HF or with recombinant murine IL-1β in adult male mice.
In contrast, IL1β is a strong promoter of interstitial collagen remodeling that may contribute to ventricular dilation and heart failure in the ischemic myocardium.
The role of inflammatory signaling is discussed and TLR4 signaling, IL-1β, TNFα and IL-6 expression appears to coincide with the development of heart failure.
Besides this, the influence of mental stress on heart failure is poorly documented despite its effects on sympathetic stimulation of interleukin-1β (IL-1β) secretion.
Our main findings were (i) patients with acute post-myocardial infarction (MI) HF (n = 236) and chronic HF (n = 150) had elevated serum levels of NGAL (determined by enzyme immunoassay), significantly correlated with clinical and neurohormonal deterioration, (ii) in patients with HF following acute MI, elevated NGAL levels of at baseline were associated with adverse outcomes (median of 27 months follow-up), (iii) in a rat model of post-MI HF, NGAL/lipocalin-2 gene expression was increased in the non-ischaemic part of the left ventricle primarily located to cardiomyocytes, (iv) strong NGAL immunostaining was found in cardiomyocytes within the failing myocardium both in experimental and clinical HF, (v) interleukin-1beta and agonists for toll-like receptors 2 and 4, representing components of the innate immune system, were potent inducers of NGAL/lipocalin-2 in isolated neonatal cardiomyocytes.