Interleukin-1 and the NLRP3 Inflammasome in Pericardial Disease

Vecchiè, Alessandra; Buono, Marco Giuseppe Del; Chiabrando, Guido Juan; Dentali, Francesco; Abbate, Antonio; Bonaventura, Aldo

doi:10.1007/s11886-021-01589-x

Cited by 19 publications

(15 citation statements)

References 66 publications

(114 reference statements)

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“…Colchicine reduced systemic inflammation, as evidenced by the reduced serum CRP on Day 2. Colchicine was shown to reduce, among other effects, inflammasome activation in patients with chronic coronary disease [23,24], acute and recurrent pericarditis [25], and low-grade inflammation related to obesity [26]. There was a concomitant reduction in circulating IL-6 and CRP in all these scenarios.…”

Section: Discussionmentioning

confidence: 99%

Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients

et al. 2023

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Objective To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. Methods We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1β, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. Results Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1β. Conclusion Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. Trial registration numbers RBR-8jyhxh

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Section: Discussionmentioning

confidence: 99%

Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients

et al. 2023

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“…The most common AE in patients treated with anakinra was a local skin reaction at the injection site (95% patients). IRAP study [70] Multicenter observational cohort study Anakinra 100 mg daily subcutaneously 224 patients with glucocorticoiddependent and colchicine-resistant recurrent pericarditis Recurrences occurred in 35% (n = 78/224) patients with a median flare-free of 10 months (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

Section: Wohlford Et Al [69]mentioning

confidence: 99%

Novel Pathophysiological, Diagnostic and Therapeutic Concepts in Acute and Recurrent Pericarditis

Bonaventura¹,

Thomas²,

Golino³

et al. 2023

Rev. Cardiovasc. Med.

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Acute pericarditis is the most frequent pericardial disease characterized by inflammation of the pericardial layers resulting in pain, dyspnea and fatigue. Often limited to an isolated event, up to 30% of patients experience one or more recurrences. There is limited knowledge about the pathophysiology of this disease, possibly due to the limited availability of animal models. More recently, following seminal clinical trials with colchicine and interleukin-1 (IL-1) blockers and a novel murine model of acute pericarditis using zymosan A, it has become clear that the NLRP3 (NACHT, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome/IL-1β axis plays a central role in driving acute pericardial inflammation and in sustaining this process during recurrences. Diagnostic management of pericarditis has been implemented with multimodality imaging including echocardiography, cardiac computed tomography, and cardiac magnetic resonance. These imaging modalities provide essential diagnostic and pathogenetic information, and are able to characterize pericardial inflammation, allowing to refine risk stratification and personalize treatment. Recent acquisitions yield relevant implications with regard to the therapeutic management of acute and recurrent pericarditis. Non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are cornerstone therapies either for acute and recurrent pericarditis. However, the benefits of targeted agents, such as anakinra -a recombinant human IL-1 receptor antagonist -and rilonacept -an IL-1α/IL-1β trap, are being increasingly recognized. To this end, phenotyping patients with pericarditis and addressing such therapies to those presenting with auto-inflammatory features (elevated C-reactive protein, sustained pericardial and systemic inflammation, multiple recurrences) is of utmost importance to identify patients who might be more likely to benefit from NLRP3 inflammasome/IL-1β pathway blockade.

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“…Интересно, что увеличение концентрации АИД и АСА у пациентов с перикардитом коррелировало с рецидивированием и риском госпитализации. В перикардиальной жидкости (но не в сыворотке) у пациентов с ИРП обнаружено увеличение концентрации провоспалительных цитокинов -интерлейкина (ИЛ) 6, ИЛ-8 и интерферона (ИФН) γ [35,36], а у пациентов с вирусным перикардитом -фактора некроза опухоли α (ФНО-α) [36]. Клиническое значение перечисленных иммунных нарушений не ясно и требует дальнейшего изучения.…”

Section: иммунопатология перикардитаunclassified

Problems of immunopathology and prospects for pharmacotherapy of idiopathic recurrent pericarditis: Using an interleukin 1 inhibitor (Anakinra)

Насонов

Sukmarova²,

Попкова³

et al. 2023

Naučno-praktičeskaâ revmatologiâ

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Pericarditis, a clinical syndrome characterized by inflammation and thickening of the pericardium, is one of the most common forms of inflammatory diseases of the cardiovascular system. The most common and severe complication of acute pericarditis is idiopathic recurrent pericarditis (IRP), which has a poor prognosis associated with the risk of cardiac tamponade and constrictive pericarditis. The pathogenesis of pericarditis is associated with a complex interaction of environmental factors, genetic predisposition, and pathological activation of innate and acquired immunity. Autoinflammatory mechanisms associated with hyperproduction of interleukin (IL) 1 attract particular attention. Standard therapy for pericarditis includes non-steroidal antiinflammatory drugs, colchicine, glucocorticoids, and immunosuppressive drugs. A new direction in the pharmacotherapy of pericarditis is associated with the use of Anakinra (a recombinant non-glycosylated analog of an IL-1 receptor antagonist), which blocks the signaling of IL-1β and IL-1α. The materials of numerous studies are summarized, indicating that Anakinra is an effective drug for the treatment of patients with IRI who are resistant to standard therapy. It is assumed that the wider use of Anakinra, especially in the early stages of pericarditis, will not only improve the prognosis, but also be important for the identification of the autoinflammatory phenotype of IRI and the development of personalized therapy programs.

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Interleukin-1 and the NLRP3 Inflammasome in Pericardial Disease

Cited by 19 publications

References 66 publications

Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients

Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients

Novel Pathophysiological, Diagnostic and Therapeutic Concepts in Acute and Recurrent Pericarditis

Problems of immunopathology and prospects for pharmacotherapy of idiopathic recurrent pericarditis: Using an interleukin 1 inhibitor (Anakinra)

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