Interleukin-1 and the NLRP3 Inflammasome in Pericardial Disease

Abstract

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.

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

“…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.…”

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

“…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).…”

“…Recently, essential steps have been accomplished to enlighten the pathophysiology and therapy for acute and recurrent pericarditis. Specifically, a focus has been placed on the emerging role of both NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome and interleukin-1β (IL-1β) in driving the onset of the acute pericardial inflammation, yet further sustaining the inflammatory process during recurrences [6][7][8]. In addition, the RHAPSODY (Rilonacept in-Hibition of interleukin-1 Alpha and beta for recurrent Pericarditis: a pivotal Symptomatology and Outcomes stuDY) trial with rilonacept -an IL-1α and IL-1β trap -has shown that IL-1 blockade is able not only to resolve the acute flare of pericarditis rapidly but also to decrease the risk of recurrences [9].…”

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

“…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.…”