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Epigenetische Regulation in der Sepsis

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Epigenetic regulation in sepsis

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Zusammenfassung

Die Sepsis ist das Krankheitsbild, das aus einer schweren systemischen Immunreaktion des Körpers auf eine Infektion unterschiedlicher Ursache resultiert. Initial reagiert das Immunsystem mit einer überschießenden Aktivierung von Entzündungszellen und der Ausschüttung proinflammatorischer Zytokine. Gleichzeitig wirken körpereigene Mechanismen durch antiinflammatorische Mediatoren und Immunzellen dieser generalisierten Entzündungsreaktion als Gegenregulation entgegen. Auch diese kompensatorische antiinflammatorische Immunantwort kann entsprechend der proinflammatorischen Reaktion übersteigert sein und resultiert dann in einer prolongierten sepsisinduzierten Immunsuppression. Die Gründe für eine solche persistierende antiinflammatorische Reaktion und die daraus folgende Vulnerabilität sind unklar. Allerdings gibt es Hinweise, dass ein septisches Ereignis die Grundeigenschaften der Immunzellen durch epigenetische Modifikation verändert. Veränderungen von Histonmodifikationen und Änderungen der Aktivierungsmechanismen von Transkriptionsfaktoren scheinen dabei in vielen Zellen des Immunsystems, wie Makrophagen, wichtige Rollen zu spielen sowie dadurch die Genregulation und Transkriptionsmechanismen der Zelle zu beeinflussen. Dieser Beitrag gibt einen Überblick über den aktuellen Stand der epigenetischen Sepsisforschung und über bisherige Erkenntnisse zu den langfristigen Auswirkungen der Sepsis auf das Immunsystem.

Abstract

Sepsis is known to be a severe systemic immune reaction based on an infection of various origins. The initial immune response is accompanied by excess activation of immune cells and release of proinflammatory cytokines. Simultaneously initiated compensatory mechanisms lead to high levels of anti-inflammatory mediators to counterbalance the generalized inflammatory reaction; however, the compensatory immunoreaction itself equally overreacts and results in a prolonged sepsis-induced immunosuppression. The underlying mechanisms for these exaggerated immune responses and the resulting global immunosuppression that increase the risk for secondary infection are still unknown. Recent findings indicate that epigenetic mechanisms change basic properties of important immune cells by mechanisms leading to changes in gene expression. Dynamic exchanges of histone modifications result in a variation of transcription and seem to play a key role in cell function of macrophages and other immune cells. This article provides a current overview of epigenetic sepsis research and the sepsis-induced effects on the immune system.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. S. Weiterer, F. Uhle, B.H. Siegler, C. Lichtenstern, M. Bartkuhn, M.A. Weigand geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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  1. Klinik für Anästhesiologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland

    S. Weiterer, F. Uhle, B.H. Siegler, C. Lichtenstern & M.A. Weigand

  2. Deutsches Zentrum für Infektionsforschung e. V. (DZIF), Standort Gießen-Marburg-Langen, Gießen, Deutschland

    S. Weiterer & M.A. Weigand

  3. Institut für Genetik, Justus-Liebig-Universität, Gießen, Deutschland

    M. Bartkuhn

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  1. S. Weiterer
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  2. F. Uhle
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Weiterer, S., Uhle, F., Siegler, B. et al. Epigenetische Regulation in der Sepsis. Anaesthesist 64, 42–55 (2015). https://doi.org/10.1007/s00101-014-2402-z

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