The Role of NLRP3 Inflammasome in Pericarditis

Mauro, Adolfo G; Bonaventura, Aldo; Vecchiè, Alessandra; Mezzaroma, Eleonora; Carbone, Salvatore; Narayan, Pratyush; Potere, Nicola; Cannatà, Antonio; Paolini, John F.; Bussani, Rossana; Montecucco, Fabrizio; Sinagra, Gianfranco; Tassel, Benjamin W. Van; Abbate, Antonio; Toldo, Stefano

doi:10.1016/j.jacbts.2020.11.016

Cited by 48 publications

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“…1 ). In samples from patients with chronic pericarditis experiencing an episode of acute pericarditis, activation of the NLRP3 inflammasome was more intense when compared with controls [ 32 •]. This was also confirmed in a mouse model of acute pericarditis induced by the intrapericardial instillation of zymosan A.…”

Section: The Nlrp3 Inflammasome and Interleukin-1 In Pericarditismentioning

confidence: 81%

“…Another indirect clue comes from the The Anakinra—Treatment of Recurrent Idiopathic Pericarditis (AIRTRIP) study, where anakinra, a recombinant IL-1 Ra, was highly effective in reducing the risk of pericarditis recurrences in patients who were colchicine-resistant and glucocorticoid-dependent [ 17 ]. Recently, Mauro et al showed that the NLRP3 inflammasome is activated within the inflamed pericardium [ 32 •] (Fig. 1 ).…”

Section: The Nlrp3 Inflammasome and Interleukin-1 In Pericarditismentioning

confidence: 99%

“…After 7 days from the acute injury, the presence of the three components of the inflammasome was markedly increased in the pericardium of zymosan A-treated mice compared with sham mice. As a further proof of it, treatment with colchicine, anakinra, and rilonacept (a dimeric fusion protein blocking IL-1α and IL-1β) was able to strongly reduce the expression of ASC, meaning that the NLRP3 inflammasome is neither oligomerized nor activated [ 32 •]. This effect was also observed by treating mice with a specific NLRP3 inhibitor that was able to reduce pericardial effusion and thickness and ASC expression.…”

Section: The Nlrp3 Inflammasome and Interleukin-1 In Pericarditismentioning

confidence: 99%

“…Original magnification for all pictures is × 40. ([ 32 •] Reproduced with permission from: Mauro AG et al JACC Basic Transl Sci. 2021;6(2):137–50; with permission from Elsevier) …”

Section: The Nlrp3 Inflammasome and Interleukin-1 In Pericarditismentioning

confidence: 99%

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Interleukin-1 and the NLRP3 Inflammasome in Pericardial Disease

Vecchiè¹,

Buono

Chiabrando

et al. 2021

Curr Cardiol Rep

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Purpose of Review Pericarditis is a generally benign disease, although complications and/or recurrences may occur in up to 30% of cases. New evidence on the pathophysiology of the disease has accumulated in recent years. Recent Findings Recently, it has been shown that the activation of the NLRP3 (NACHT, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome is central in the pathophysiology of pericarditis. These findings derive from clinical data, an experimental animal model of acute pericarditis supporting a role for the NLRP3 inflammasome in pericarditis, and from indirect evidence of inhibitors of NLRP3 inflammasome in clinical trials. Summary Pericarditis is regarded as a stereotypical response to an acute damage of the mesothelial cells of the pericardial layers. NLRP3 inflammasome, a macromolecular structure sensing damage and releasing pro-inflammatory cytokines, is centrally involved as it releases interleukin (IL)-1β, whose auto-induction feeds an autoinflammatory disease, mostly responsible for recurrences. Colchicine, an inhibitor of NLRP3 inflammasome formation, and IL-1-targeted therapies, such as anakinra and rilonacept, were found to effectively blunt the acute inflammation and reduce the risk for recurrences.

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Section: The Nlrp3 Inflammasome and Interleukin-1 In Pericarditismentioning

confidence: 81%

Section: The Nlrp3 Inflammasome and Interleukin-1 In Pericarditismentioning

confidence: 99%

Section: The Nlrp3 Inflammasome and Interleukin-1 In Pericarditismentioning

confidence: 99%

“…Original magnification for all pictures is × 40. ([ 32 •] Reproduced with permission from: Mauro AG et al JACC Basic Transl Sci. 2021;6(2):137–50; with permission from Elsevier) …”

Section: The Nlrp3 Inflammasome and Interleukin-1 In Pericarditismentioning

confidence: 99%

See 2 more Smart Citations

Interleukin-1 and the NLRP3 Inflammasome in Pericardial Disease

Vecchiè¹,

Buono

Chiabrando

et al. 2021

Curr Cardiol Rep

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“…An NLRP3 inflammasome inhibitor (16673–34–0) is being investigated for pericarditis. Preliminary data suggest that 16673–34–0 is associated with reducing pericardial effusions when combined with colchicine and with reducing pericardial thickening 59 . In addition to CRP monitoring, IL‐6 monitoring may also have some utility in effecting the prognosis and outcomes of patients with pericarditis 60 …”

Section: Future Directionsmentioning

confidence: 99%

Current pharmacotherapy management of children and adults with pericarditis: Prospectus for improved outcomes

et al. 2021

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Pericarditis is the most common inflammatory pericardial disease in both children and adults. Since the 2015 European Society of Cardiology Guidelines for the diagnosis and management of pericardial disease were published, there have been significant updates to management. Pharmacotherapy has been historically reserved for idiopathic pericarditis (IP). However, there has been increasing use of pharmacotherapies, such as anti‐inflammatory therapies, colchicine, and immunotherapies for other causes of pericarditis, such as post‐cardiac injury syndromes (PCIS). Nevertheless, the quality of data varies depending on PCIS or idiopathic etiologies, as well as the adult and pediatric population. High‐dose anti‐inflammatory therapies should be used to manage symptoms associated with either etiology of pericarditis in both adults and children, but do not ameliorate the inflammatory disease process. Choice of anti‐inflammatory should be guided by drug‐drug/disease interactions, cost, tolerability, patient age, and should be tapered accordingly over several weeks to months. Colchicine should be added as adjuvant therapy to anti‐inflammatory therapies in adults and children with IP, as it has been shown to lower the risk of recurrence, reduce pericarditis symptoms, and improve morbidity. Colchicine is also reasonable to add to adults and children with pericarditis secondary to PCIS. Systemic glucocorticoids increase risk of recurrence in adults and children with IP and are reserved for second‐line treatment in acute and recurrent IP; they are generally avoided in PCIS. Immunotherapies are regarded as third‐line for recurrent IP in adults and children. Limited evidence exists to support their use in patients with pericarditis from PCIS. Pharmacovigilance strategies, such as C‐reactive protein and adverse drug event monitoring, are also important toward balancing efficacy and safety of the various strategies used to manage pericarditis in adults and children.

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Variants at the Interleukin 1 Gene Locus and Pericarditis

Thorolfsdottir,

Jonsdottir,

Sveinbjornsson

et al. 2024

JAMA Cardiol

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ImportanceRecurrent pericarditis is a treatment challenge and often a debilitating condition. Drugs inhibiting interleukin 1 cytokines are a promising new treatment option, but their use is based on scarce biological evidence and clinical trials of modest sizes, and the contributions of innate and adaptive immune processes to the pathophysiology are incompletely understood.ObjectiveTo use human genomics, transcriptomics, and proteomics to shed light on the pathogenesis of pericarditis.Design, Setting, and ParticipantsThis was a meta-analysis of genome-wide association studies of pericarditis from 5 countries. Associations were examined between the pericarditis-associated variants and pericarditis subtypes (including recurrent pericarditis) and secondary phenotypes. To explore mechanisms, associations with messenger RNA expression (cis-eQTL), plasma protein levels (pQTL), and CpG methylation of DNA (ASM-QTL) were assessed. Data from Iceland (deCODE genetics, 1983-2020), Denmark (Copenhagen Hospital Biobank/Danish Blood Donor Study, 1977-2022), the UK (UK Biobank, 1953-2021), the US (Intermountain, 1996-2022), and Finland (FinnGen, 1970-2022) were included. Data were analyzed from September 2022 to August 2023.ExposureGenotype.Main Outcomes and MeasuresPericarditis.ResultsIn this genome-wide association study of 4894 individuals with pericarditis (mean [SD] age at diagnosis, 51.4 [17.9] years, 2734 [67.6%] male, excluding the FinnGen cohort), associations were identified with 2 independent common intergenic variants at the interleukin 1 locus on chromosome 2q14. The lead variant was rs12992780 (T) (effect allele frequency [EAF], 31%-40%; odds ratio [OR], 0.83; 95% CI, 0.79-0.87; P = 6.67 × 10−16), downstream of IL1B and the secondary variant rs7575402 (A or T) (EAF, 45%-55%; adjusted OR, 0.89; 95% CI, 0.85-0.93; adjusted P = 9.6 × 10−8). The lead variant rs12992780 had a smaller odds ratio for recurrent pericarditis (0.76) than the acute form (0.86) (P for heterogeneity = .03) and rs7575402 was associated with CpG methylation overlapping binding sites of 4 transcription factors known to regulate interleukin 1 production: PU.1 (encoded by SPI1), STAT1, STAT3, and CCAAT/enhancer-binding protein β (encoded by CEBPB).Conclusions and RelevanceThis study found an association between pericarditis and 2 independent sequence variants at the interleukin 1 gene locus. This finding has the potential to contribute to development of more targeted and personalized therapy of pericarditis with interleukin 1–blocking drugs.

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The Role of NLRP3 Inflammasome in Pericarditis

Abstract: Visual Abstract

Cited by 48 publications

References 49 publications

Interleukin-1 and the NLRP3 Inflammasome in Pericardial Disease

Interleukin-1 and the NLRP3 Inflammasome in Pericardial Disease

Current pharmacotherapy management of children and adults with pericarditis: Prospectus for improved outcomes

Variants at the Interleukin 1 Gene Locus and Pericarditis

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