Abstract:IMPORTANCEIn the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial, the anti-inflammatory monoclonal antibody canakinumab significantly reduced the risk of recurrent cardiovascular events in patients with previous myocardial infarction (MI) and high-sensitivity C-reactive protein (hs-CRP) levels of 2 mg/L or greater.OBJECTIVE To estimate the cost-effectiveness of adding canakinumab to standard of care for the secondary prevention of major cardiovascular events over a range of potential pric… Show more
“…First, safety issues such as immunosuppression that might increase the susceptibility to infections and tumors (8,31). And second, the high costs [for example of biological drugs; (32,33)] and the logistic and technical limitations [for example of cellular therapies; (34)] that make unrealistic the translation of the agents to routine prophylactic or therapeutic clinical use.…”
Ospina-Quintero et al. Regulatory Cell-Inducing Small Molecule Formulation non-immunosuppressive, low-dose of VitD/Dexa, administered subcutaneously and repetitively, exerts atheroprotective effects in dyslipidemic mice, apparently due to the induction of an IL-10-producing network of lymphoid and myeloid immune cells. These well known, widely available, and inexpensive small molecules can be easily coformulated into a simple and accessible agent with a potential use as a prophylactic or therapeutic immune intervention for CVD and other chronic inflammatory diseases.
“…First, safety issues such as immunosuppression that might increase the susceptibility to infections and tumors (8,31). And second, the high costs [for example of biological drugs; (32,33)] and the logistic and technical limitations [for example of cellular therapies; (34)] that make unrealistic the translation of the agents to routine prophylactic or therapeutic clinical use.…”
Ospina-Quintero et al. Regulatory Cell-Inducing Small Molecule Formulation non-immunosuppressive, low-dose of VitD/Dexa, administered subcutaneously and repetitively, exerts atheroprotective effects in dyslipidemic mice, apparently due to the induction of an IL-10-producing network of lymphoid and myeloid immune cells. These well known, widely available, and inexpensive small molecules can be easily coformulated into a simple and accessible agent with a potential use as a prophylactic or therapeutic immune intervention for CVD and other chronic inflammatory diseases.
BackgroundDyslipidemia and inflammation are closely interrelated contributors in the pathogenesis of atherosclerosis. Disorders of lipid metabolism initiate an inflammatory and immune-mediated response in atherosclerosis, while low-density lipoprotein cholesterol (LDL-C) lowering has possible pleiotropic anti-inflammatory effects that extend beyond lipid lowering.Main textActivation of the immune system/inflammasome destabilizes the plaque, which makes it vulnerable to rupture, resulting in major adverse cardiac events (MACE). The activated immune system potentially accelerates atherosclerosis, and atherosclerosis activates the immune system, creating a vicious circle. LDL-C enhances inflammation, which can be measured through multiple parameters like high-sensitivity C-reactive protein (hsCRP). However, multiple studies have shown that CRP is a marker of residual risk and not, itself, a causal factor. Recently, anti-inflammatory therapy has been shown to decelerate atherosclerosis, resulting in fewer MACE. Nevertheless, an important side effect of anti-inflammatory therapy is the potential for increased infection risk, stressing the importance of only targeting patients with high residual inflammatory risk. Multiple (auto-)inflammatory diseases are potentially related to/influenced by LDL-C through inflammasome activation.ConclusionsResearch suggests that LDL-C induces inflammation; inflammation is of proven importance in atherosclerotic disease progression; anti-inflammatory therapies yield promise in lowering (cardiovascular) disease risk, especially in selected patients with high (remaining) inflammatory risk; and intriguing new anti-inflammatory developments, for example, in nucleotide-binding leucine-rich repeat-containing pyrine receptor inflammasome targeting, are currently underway, including novel pathway interventions such as immune cell targeting and epigenetic interference. Long-term safety should be carefully monitored for these new strategies and cost-effectiveness carefully evaluated.
“…However, none of the IL-1ď˘ blockers have been approved for clinical application in patients with MI at the present time. That includes Canakinumab (Ilaris), an IL-1ď˘ antibody that entered the clinical stage [Anti-Inflammatory Thrombosis Outcomes Study (CANTOS)] in 2017 (10,11). One major reason for the lack of successful clinical candidates is the risky safety profile of IL-1ď˘ blockers.…”
An acute myocardial infarction (AMI) induces a sterile inflammatory response that facilitates further heart injury and promotes adverse cardiac remodeling. Interleukin-1β (IL-1β) plays a central role in the sterile inflammatory response that results from AMI. Thus, IL-1β blockage is a promising strategy for treatment of AMI. However, conventional IL-1β blockers lack targeting specificity. This increases the risk of serious side effects. To address this problem herein, we fabricated platelet microparticles (PMs) armed with antiâIL-1β antibodies to neutralize IL-1β after AMI and to prevent adverse cardiac remodeling. Our results indicate that the infarct-targeting PMs could bind to the injured heart, increasing the number of antiâIL-1β antibodies therein. The antiâIL-1β platelet PMs (IL1-PMs) protect the cardiomyocytes from apoptosis by neutralizing IL-1β and decreasing IL-1βâdriven caspase-3 activity. Our findings indicate that IL1-PM is a promising cardiac detoxification agent that removes cytotoxic IL-1β during AMI and induces therapeutic cardiac repair.
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