Interleukin-1 Blockade in Acute Myocardial Infarction and Heart Failure

Toldo, Stefano; Tassell, Benjamín W. Van; Abbate, Antonio

doi:10.1016/j.jacbts.2017.07.006

Cited by 13 publications

(7 citation statements)

References 16 publications

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“…Previous studies have shown that CFs express PRRs that recognize pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns, and venom-associated molecular patterns (VAMPs) 2,[19][20][21] , and the increase in NLRP3 expression in CFs has been implicated in the size of the infarcted area during ischemia/reperfusion 22 , and is crucial for cardiac dysfunction during sepsis 23 . Interestingly, the role of IL-1β in cardiac dysfunction has already been demonstrated in previous studies 20, [24][25][26][27] , given that this cytokine can desensitize cardiomyocytes after adrenergic stimulation and induce reversible contractile dysfunction in the cardiac muscle along with arrhythmias 24 . However, in addition to the mediators produced by the heart cells, we also have to consider the contribution of PGE 2 and IL-1β produced both systemically and by the lungs to cardiac dysfunction.…”

Section: Discussionmentioning

confidence: 69%

Interleukin-1 receptor-induced PGE2 production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation

Reis¹,

Rodrigues

Lautherbach

et al. 2020

Nat Commun

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Scorpion envenomation is a leading cause of morbidity and mortality among accidents caused by venomous animals. Major clinical manifestations that precede death after scorpion envenomation include heart failure and pulmonary edema. Here, we demonstrate that cardiac dysfunction and fatal outcomes caused by lethal scorpion envenomation in mice are mediated by a neuro-immune interaction linking IL-1 receptor signaling, prostaglandin E2, and acetylcholine release. IL-1R deficiency, the treatment with a high dose of dexamethasone or blockage of parasympathetic signaling using atropine or vagotomy, abolished heart failure and mortality of envenomed mice. Therefore, we propose the use of dexamethasone administration very early after envenomation, even before antiserum, to inhibit the production of inflammatory mediators and acetylcholine release, and to reduce the risk of death.

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Section: Discussionmentioning

confidence: 69%

Interleukin-1 receptor-induced PGE2 production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation

Reis¹,

Rodrigues

Lautherbach

et al. 2020

Nat Commun

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“…This points to a different role and timing of action of the two isoforms of IL-1, IL-1␣ and IL-1␤. In a recent preclinical study in diabetic rats, administration of gevokizumab, a monoclonal antibody against IL-1␤, limited the progression of HF after MI and reduced oxidative stress, ventricular remodeling, scar size, and coronary endotheliumdependent relaxation, independent of infarct size (60,134).…”

Section: Blockade Of Il-1␣ and Il-1␤ In Amimentioning

confidence: 99%

Inflammasome, pyroptosis, and cytokines in myocardial ischemia-reperfusion injury

Toldo

Mauro²,

Cutter³

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

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284

213

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Myocardial ischemia reperfusion induces a sterile inflammatory response leading to further injury that contributed to the final infarct size. Locally released danger associated molecular patterns (DAMPs) lead to priming and triggering of the Nod-like receptor protein 3 (NLRP3) inflammasome and amplification of the inflammatory response and of cell death by activation of caspase-1. In this review, we examine strategies inhibiting the priming, triggering, or caspase-1 activity, or blockade of the inflammasome-related cytokines, Interleukin-1β (IL-1β) and IL-18, focusing on the beneficial effects seen in experimental models of AMI in animals, and the initial results of clinical translational research trials.

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“…Specifically, the acidification of the environment cause macrophages to increase the secretion of the pro-inflammatory cytokines IL-1β and IL-18 (54). Since IL-1 antagonist therapies are being developed for the treatment of MI (55–57), the use of a pH-sensitive drug delivery hydrogel system in a context where IL-1 levels are elevated would potentially be an effective and novel anti-inflammatory therapeutic strategy.…”

Section: Design Of Injectable Biomaterials For Cardiac Tissue Engineementioning

confidence: 99%

Toward Regeneration of the Heart: Bioengineering Strategies for Immunomodulation

Ferrini

Stevens

Sattler

et al. 2019

Front. Cardiovasc. Med.

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Myocardial Infarction (MI) is the most common cardiovascular disease. An average-sized MI causes the loss of up to 1 billion cardiomyocytes and the adult heart lacks the capacity to replace them. Although post-MI treatment has dramatically improved survival rates over the last few decades, more than 20% of patients affected by MI will subsequently develop heart failure (HF), an incurable condition where the contracting myocardium is transformed into an akinetic, fibrotic scar, unable to meet the body's need for blood supply. Excessive inflammation and persistent immune auto-reactivity have been suggested to contribute to post-MI tissue damage and exacerbate HF development. Two newly emerging fields of biomedical research, immunomodulatory therapies and cardiac bioengineering, provide potential options to target the causative mechanisms underlying HF development. Combining these two fields to develop biomaterials for delivery of immunomodulatory bioactive molecules holds great promise for HF therapy. Specifically, minimally invasive delivery of injectable hydrogels, loaded with bioactive factors with angiogenic, proliferative, anti-apoptotic and immunomodulatory functions, is a promising route for influencing the cascade of immune events post-MI, preventing adverse left ventricular remodeling, and offering protection from early inflammation to fibrosis. Here we provide an updated overview on the main injectable hydrogel systems and bioactive factors that have been tested in animal models with promising results and discuss the challenges to be addressed for accelerating the development of these novel therapeutic strategies.

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Interleukin-1 Blockade in Acute Myocardial Infarction and Heart Failure

Abstract: Corresponding Author

Cited by 13 publications

References 16 publications

Interleukin-1 receptor-induced PGE2 production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation

Interleukin-1 receptor-induced PGE2 production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation

Inflammasome, pyroptosis, and cytokines in myocardial ischemia-reperfusion injury

Toward Regeneration of the Heart: Bioengineering Strategies for Immunomodulation

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