The IL-1β Antibody Gevokizumab Limits Cardiac Remodeling and Coronary Dysfunction in Rats With Heart Failure

Harouki, BS Najah; Nicol, Lionel; Rémy-Jouet, Isabelle; Henry, BS Jean-Paul; Dumesnil, BS Anais; Lejeune, BS Annie; Renet, BS Sylvanie; Golding, BS Francesca; Djerada, Zoubir; Wecker, Didier; Bolduc, Virginie; Bouly, Muriel; Roussel, Jérôme; Richard, Vincent; Mulder, Paul

doi:10.1016/j.jacbts.2017.06.005

Cited by 59 publications

(35 citation statements)

References 55 publications

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“…To capture the IL-1, a potent monoclonal antibody, Gevokizumab, was used. Gevokizumab (also called XOMA 052 and developed by XOMA Corporation) is an antiinflammatory agent that has been used in clinical trials to treat acne vulgaris, osteoarthritis, Bechet's uveitis, pyoderma gangrenosum, and Bechet's disease (19)(20)(21). It was first modified for the binding of platelets using 1,2-distearoyl-sn-glycero-3-phosphoethanolaminepoly(ethylene glycol) (DSPE-PEG) derivatives.…”

Section: Introductionmentioning

confidence: 99%

Targeted anti–IL-1β platelet microparticles for cardiac detoxing and repair

Huang

et al. 2020

Sci. Adv.

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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 anti–IL-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 anti–IL-1β antibodies therein. The anti–IL-1β platelet PMs (IL1-PMs) protect the cardiomyocytes from apoptosis by neutralizing IL-1β and decreasing IL-1β–driven 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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Section: Introductionmentioning

confidence: 99%

Targeted anti–IL-1β platelet microparticles for cardiac detoxing and repair

Huang

et al. 2020

Sci. Adv.

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“…In this issue of JACC: Basic to Translational Science , Harouki et al. (5) show that neutralization of IL-1β using the monoclonal antibody gevokizumab initiated shortly after reperfusion (1 h) or late (7 days) significantly improved cardiac remodeling and systolic and diastolic function in nondiabetic as well as diabetic rats with AMI due to ischemia-reperfusion injury. Furthermore, when gevokizumab was administered 83 days after reperfusion, and when cardiac dilation and dysfunction had already been established, IL-1β blockade resulted in an improvement in systolic function.…”

mentioning

confidence: 99%

Interleukin-1 Blockade in Acute Myocardial Infarction and Heart Failure

Toldo¹,

Tassell²,

Abbate

2017

JACC: Basic to Translational Science

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“…Existing studies suggest that during hospitalization for acute decompensated HF, circulating IL‐1β levels are associated with a higher concentration of natriuretic peptides (myocardial stretch) and troponin T (myocardial injury), along with a higher hazard of death at 1 year . Further, in murine models, administration of anti‐IL‐1β antibody given early or late after reperfused myocardial infarction improved LV remodelling and function . These findings, the benefits seen with canakinumab in reducing cardiovascular outcomes, and incident HF after myocardial infarction identify IL‐1β as an especially promising therapeutic target for immunomodulation.…”

Section: Discussionmentioning

confidence: 89%

Effect of immunomodulation on cardiac remodelling and outcomes in heart failure: a quantitative synthesis of the literature

et al. 2020

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Aims Immunomodulation in heart failure (HF) has been studied in several randomized controlled trials (RCTs) with variable effects on cardiac structure, function, and outcomes. We sought to determine the effect of immunomodulation on left ventricular ejection fraction (LVEF), LV end-diastolic dimension (LVEDD), and all-cause mortality in patients with HF with reduced ejection fraction (HFrEF) through meta-analyses and trial sequential analyses (TSAs) of RCTs. Methods and results PubMed, Embase®, Cochrane CENTRAL, and ClinicalTrials.gov were systematically reviewed to identify RCTs that studied the effects of immunomodulation in patients with HFrEF. The primary endpoint in this analysis was change in LVEF. Secondary outcomes were changes in LVEDD and all-cause mortality. TSA was used to quantify the statistical reliability of data in the cumulative meta-analyses. Nineteen RCTs with 1341 HFrEF subjects were eligible for analyses. The aetiology of HF, specific immunomodulation strategy, and treatment duration were variable across trials. Immunomodulation led to a greater improvement in LVEF [mean difference: +5.7% 95% confidence interval (CI): 3.0-8.5%, P < 0.001] and reduction in LVEDD (mean difference: À3.7 mm, 95% CI: À7.0 to À0.4 mm, P = 0.028) than no immunomodulation in meta-analyses and TSAs. We observed a non-significant decrease in all-cause mortality among those on immumomodulation (risk ratio: 0.7, 95% CI: 0.4-1.3, P = 0.234), but the Z-curve for cumulative treatment effect of immunomodulation in the TSA did not cross the boundary of futility. Conclusions Immunomodulation led to improved cardiac structure and function in patients with HFrEF. While these benefits did not translate into a significant improvement in mortality, our analysis suggests that larger studies of targeted immunomodulation are needed to understand the true benefits.

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The IL-1β Antibody Gevokizumab Limits Cardiac Remodeling and Coronary Dysfunction in Rats With Heart Failure

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Cited by 59 publications

References 55 publications

Targeted anti–IL-1β platelet microparticles for cardiac detoxing and repair

Targeted anti–IL-1β platelet microparticles for cardiac detoxing and repair

Interleukin-1 Blockade in Acute Myocardial Infarction and Heart Failure

Effect of immunomodulation on cardiac remodelling and outcomes in heart failure: a quantitative synthesis of the literature

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