Recombinant Human Interleukin-1 Receptor Antagonist Provides Cardioprotection During Myocardial Ischemia Reperfusion in the Mouse

Toldo, Stefano; Schatz, Aaron; Mezzaroma, Eleonora; Chawla, Raveen; Stallard, Thomas W.; Stallard, William C.; Jahangiri, Arehzo; Tassell, Benjamín W. Van; Abbate, Antonio

doi:10.1007/s10557-012-6389-x

Cited by 36 publications

(14 citation statements)

References 8 publications

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“…The formation of the inflammasome induces caspase-1 activation, which leads to the processing of pro-IL-1β and pro-IL-18 from their inactive forms into mature secreted cytokines28. Recently, inflammasome-derived cytokines IL-1β and IL-18 have been shown to modulate the cardiac remodeling process after injury and depress myocardial function30313233. Accordingly, it is not surprising that in our remnant kidney model, an upregulation of cardiac NLRP3 inflammasome components were observed in addition to a significant increase of circulating IL-1β levels.…”

Section: Discussionmentioning

confidence: 99%

Suppression of NLRP3 Inflammasome Activation Ameliorates Chronic Kidney Disease-Induced Cardiac Fibrosis and Diastolic Dysfunction

Bugyei-Twum

Abadeh

Thai

et al. 2016

Sci Rep

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Cardiac fibrosis is a common finding in patients with chronic kidney disease. Here, we investigate the cardio-renal effects of theracurmin, a novel formulation of the polyphenolic compound curcumin, in a rat model of chronic kidney disease. Briefly, Sprague-Dawley rats were randomized to undergo sham or subtotal nephrectomy (SNx) surgery. At 3 weeks post surgery, SNx animals were further randomized to received theracurmin via once daily oral gavage or vehicle for 5 consecutive weeks. At 8 weeks post surgery, cardiac function was assessed via echocardiography and pressure volume loop analysis, followed by LV and renal tissue collection for analysis. SNx animals developed key hallmarks of renal injury including hypertension, proteinuria, elevated blood urea nitrogen, and glomerulosclerosis. Renal injury in SNx animals was also associated with significant diastolic dysfunction, macrophage infiltration, and cardiac NLRP3 inflammasome activation. Treatment of SNx animals with theracurmin improved structural and functional manifestations of cardiac injury associated with renal failure and also attenuated cardiac NLRP3 inflammasome activation and mature IL-1β release. Taken together, our findings suggest a significant role for the NLRP3 inflammasome in renal injury-induced cardiac dysfunction and presents inflammasome attenuation as a unique strategy to prevent adverse cardiac remodeling in the setting of chronic kidney disease.

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Section: Discussionmentioning

confidence: 99%

Suppression of NLRP3 Inflammasome Activation Ameliorates Chronic Kidney Disease-Induced Cardiac Fibrosis and Diastolic Dysfunction

Bugyei-Twum

Abadeh

Thai

et al. 2016

Sci Rep

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“…NEC1 is protective in sterile injury models such as ischemia/reperfusion injury in the heart (32) and the brain (23, 33), paradigms of injury in which IL-1 blockade is also protective (34, 35). RIP1-dependent production of IL-1α has been linked to inflammatory tissue damage in a genetic mouse model of inflammation, although in this instance the production of IL-1α was independent of RIP3 and necroptotic cell death (36).…”

Section: Discussionmentioning

confidence: 99%

Release of Interleukin-1α or Interleukin-1β Depends on Mechanism of Cell Death

England

Summersgill

Edye

et al. 2014

Journal of Biological Chemistry

139

114

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Background: Cell death is a regulator of inflammation via the master cytokine IL-1.Results: Apoptotic stimuli induced a caspase-8-dependent release of IL-1β from macrophages. Necroptotic stimuli induced a calpain-dependent release of IL-1α.Conclusion: Mechanisms of cell death dictate the nature and form of IL-1 release.Significance: Sterile inflammatory responses may be determined by the mechanisms of cell death potentially allowing for selective interventions.

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“…This pattern of impaired healing and increased rupture was not seen in the studies using genetic models of IL-1 receptor deletion nor in the studies using pharmacologic agents to non-selectively block IL-1α and IL-1β (i.e. anakinra or IL-1 trap) 62-66, 68, 72, 74, 75 and thus raised the question of whether selective IL-1β blockade would elicit adverse effects. More recent studies using well-described IL-1β antibodies specifically developed for in vivo use have shown a protective effect of IL-1β blockade.…”

Section: Role Of Interleukin-1 In the Healing Process Following Acutementioning

confidence: 99%

Targeting Interleukin-1 in Heart Disease

et al. 2013

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Recombinant Human Interleukin-1 Receptor Antagonist Provides Cardioprotection During Myocardial Ischemia Reperfusion in the Mouse

Abstract: IL-1 blockade therapies using rhIL-1Ra prior the onset of AMI protects the myocardium and preserves cardiac function.

Cited by 36 publications

References 8 publications

Suppression of NLRP3 Inflammasome Activation Ameliorates Chronic Kidney Disease-Induced Cardiac Fibrosis and Diastolic Dysfunction

Suppression of NLRP3 Inflammasome Activation Ameliorates Chronic Kidney Disease-Induced Cardiac Fibrosis and Diastolic Dysfunction

Release of Interleukin-1α or Interleukin-1β Depends on Mechanism of Cell Death

Targeting Interleukin-1 in Heart Disease

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