Targeting the inflammasome in rheumatic diseases

McCoy, Sara S.; Stannard, Jasmine; Kahlenberg, J. Michelle

doi:10.1016/j.trsl.2015.06.006

Cited by 13 publications

(14 citation statements)

References 162 publications

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“…B. den systemischen Lupus erythematodes, die rheumatoide Arthritis, und Stoffwechselerkrankungen (z. B. Gicht) gut dokumentiert und wird durch die Wirksamkeit der gegen IL-1 oder IL-1-Rezeptor gerichteten Therapie mit Biologika wie Canakinumab, Rilonacept oder Anakinra klinisch belegt [31,32]. Enzymatisch aktive Caspase-1 vermittelt zudem einen programmierten, proinflammatorischen Zelltod, der unabhängig von apoptotischen Caspasen abläuft und als Pyroptose bekannt ist.…”

Section: Caspase-1-funktionenunclassified

“…Die Akkumulation von Uratkristallen in Gelenken bei Patienten mit Gicht führt zu einer Inflammasomaktivierung und konsekutiver Expression und Sekretion von IL-1β. Diese Erkenntnis hat bereits Einzug in den klinischen Alltag gefunden, da Patienten mit schwerer und/oder therapierefraktä-rer Gicht mit IL-1 blockierenden Medikamenten behandelt werden [31,32].…”

Section: Caspase-1-abhängige Signalwege Im Kontext Rheumatischer Erkrunclassified

“…sogar eine potenzielle primäre Beteiligung von inflammatorischen Caspasen in der Pathophysiologie von Autoimmunerkrankungen diskutiert. Neben der Expression von Autoantikörpern, der Bildung und Deposition von Immunkomplexen sowie dem Vorhandensein autoreaktiver T-Zellen scheinen bei systemischem Lupus erythematodes (SLE) oder rheumatoider Arthritis (RA) auch das Inflammasom und die dysregulierte Caspase-1-Aktivität eine Rolle in der Pathogenese zu spielen [32]. Die ausführliche Diskussion dieser Erkrankungen geht jedoch über die Zielsetzung dieses Beitrags hinaus.…”

Section: Caspase-1-abhängige Signalwege Im Kontext Rheumatischer Erkrunclassified

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Caspase-1 als Regulator der Autoinflammation bei rheumatischen Erkrankungen

2016

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Caspase-1 is an integral regulator of the innate immune system. Its core functions are the processing and secretion of the proinflammatory cytokines interleukin 1β (IL-1 beta) and IL-18 and the initiation of proinflammatory cell death, which is referred to as pyroptosis. Activation of caspase-1 plays a pivotal role during immune defense mechanisms against infections by the innate immune system. Dysregulated activation of caspase-1 has been recognized to be involved in the pathophysiology of a constantly increasing number of inflammatory diseases. This article gives an overview of the regulation and function of caspase-1 and its involvement in monogenic, polygenic and/or polyetiological rheumatic diseases.

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Section: Caspase-1-funktionenunclassified

Section: Caspase-1-abhängige Signalwege Im Kontext Rheumatischer Erkrunclassified

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Caspase-1 als Regulator der Autoinflammation bei rheumatischen Erkrankungen

2016

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“…Reversible neutropenia is also occasionally noted(5). Other IL-1 inhibitory drugs are in development (reviewed in(6, 7)) and include medications which inhibit activation of the inflammasome, the molecular complex which activates IL-1β(8). Evaluation of inhibitors of kinases downstream of the IL-1R is also under way(9, 10)*.…”

Section: Therapeutic Armamentariummentioning

confidence: 99%

Anti-inflammatory panacea? The expanding therapeutics of interleukin-1 blockade

Kahlenberg

2016

Current Opinion in Rheumatology

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Purpose of review Blockade of IL-1 signaling is one of the oldest biologic therapies, yet the use of these agents is on the rise as the role of IL-1 activation is being recognized in a wide spectrum of inflammatory disorders. This review will cover established and emerging uses of IL-1 antagonism in rheumatic diseases. Recent findings Expanding off-label indications for IL-1 blockade include neutrophil-dominant skin diseases including pyoderma gangrenosum, hidradenitis supperativa, and pustular psoriasis. There is also increasing evidence for the use of IL-1 blockade in heart failure associated with rheumatic diseases. Somatic mosaicism in NLRP3 may explain the onset of later-in-life presentations of periodic fevers which are responsive to IL-1 blockade. Of importance, clinical response to anti-IL-1 therapy does not always denote protection from autoinflammatory disease complications such as macrophage activation syndrome or amyloidosis. Summary Indications for IL-1 blocking therapies will likely continue to broaden, but given the rarity of many rheumatic diseases which respond to such treatment, rigorous, large clinical trials for each indication are unlikely to occur. Thus, recommended use of these medications will often fall to the discretion of the astute physician. However, medication cost and hurdles of insurance approval, rather than drug efficacy, may be the primary limitation for more widespread use.

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“…Several articles in this issue describe the NLRP3 inflammasome, its activation in PMNs and macrophages, and formation in PMNs of neutrophil extracellular traps (NETs) as the innate immune system responds to contain infectious agents (45, 46). Contributions of the NLRP3 inflammasome to inflammatory disorders are also described.…”

Section: The Nlrp3 Inflammasomementioning

confidence: 99%

Anti-inflammatory interventions—what has worked, not worked, and what may work in the future

Fattahi

Ward

2016

Translational Research

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Our Introductory Commentary relates to many topics that are linked to inflammatory responses and how these responses are regulated in order to promote healing of damaged tissues and bring about effective clearance of infectious agents. In non-infectious situations, cells and tissues release products (danger associated molecular patterns) that can trigger damaging inflammatory responses. These products must be effectively dealt with in order to avoid serious tissue injury. We provide a perspective about many decades of research into the inflammatory response and describe strategies that have achieved success in restraining inflammatory responses, as well as many approaches that have not been clinically effective. With development of new technologies such as advanced genomic analysis, highly sensitive and sophisticated mass spectrometry and related approaches, as well as the ability to employ mutagenesis induction, we are beginning to define highly sophisticated molecular pathways that previously were opaque. This progress may well have clinical relevance, and we may be on the edge of a scientific revolution in the broad area of inflammation.

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Targeting the inflammasome in rheumatic diseases

Cited by 13 publications

References 162 publications

Caspase-1 als Regulator der Autoinflammation bei rheumatischen Erkrankungen

Caspase-1 als Regulator der Autoinflammation bei rheumatischen Erkrankungen

Anti-inflammatory panacea? The expanding therapeutics of interleukin-1 blockade

Anti-inflammatory interventions—what has worked, not worked, and what may work in the future

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