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Kristallinduzierte Inflammasomaktivierung: Gicht und Pseudogicht

Crystal-induced activation of the inflammasome: gout and pseudogout

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Zusammenfassung

Auf Kristalle in Geweben reagiert das angeborene Immunsystem wie auf pathogene Keime. Über die Aktivierung eines Inflammasoms wird Interleukin-1 (IL-1) freigesetzt, das u. a. Cyclooxgenase, TNF und IL-8 hochreguliert und eine akute, granulozytäre Gelenkentzündung auslöst. Daher dürften neben NSAR, Steroiden und Colchicin auch IL-1-Blocker wirken. Größere klinische Studien wurden bereits initiiert. Bei Patienten mit Kontraindikationen gegen NSAR oder unzureichender Wirkung könnten diese Substanzen eine wertvolle Alternative darstellen. Ist der Gichtanfall wieder abgeklungen, ist aber weiter die Kontrolle des Harnsäurehaushalts entscheidend. Dass zumindest einige der Urattransporter, deren Störung zu Hyperurikämie führt, identifiziert wurden, könnte in Zukunft ebenfalls zu gezielten Therapieansätzen führen. Vorerst bleiben aber Diät und Hemmung der Harnsäuresynthese die Hauptangriffspunkte. Der neue Xanthinoxidasehemmer Febuxostat stellt hier eine neue Therapieoption bei Niereninsuffizienz oder Unverträglichkeit von Allopurinol dar.

Abstract

Crystals in tissues lead the innate immune system to the same kind of acute response seen with pathogens. Via activation of the inflammasome, interleukin-1 (IL-1) is released, which upregulates mediators such as cyclooxygenase, tumor necrosis factor, and IL-8 and induces an acute granulocytic inflammation. Therefore, in addition to nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, and colchicine, IL-1 blockers appear to be effective. Large clinical trials have already been initiated. Such an approach could constitute a valuable alternative for patients with contraindications or insufficient response to NSAIDs. After the attack has subsided, control of uric acid metabolism is central. At least several of the responsible urate transporters have been unraveled, which could lead to more focused therapy in the future. At present, diet and blockade of uric acid synthesis remain the main pillars of therapy. The new xanthine oxidase inhibitor febuxostat constitutes a novel option for patients with renal insufficiency or intolerance to allopurinol.

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  1. Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus, Technische Universität, Fetscherstraße 74, 01307, Dresden, Deutschland

    M. Winzer, A.-K. Tausche & M. Aringer

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  1. M. Winzer
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  2. A.-K. Tausche
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  3. M. Aringer
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Winzer, M., Tausche, AK. & Aringer, M. Kristallinduzierte Inflammasomaktivierung: Gicht und Pseudogicht. Z. Rheumatol. 68, 733–739 (2009). https://doi.org/10.1007/s00393-009-0489-4

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