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Apoptose als Pathomechanismus in der Sepsis

  • Intensivmedizin
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Zusammenfassung

Die Sepsis gehört nach wie vor zu den häufigsten Todesursachen bei Intensivpatienten. Der Pathogenese der Erkrankung liegt ein komplexes Immungeschehen zugrunde. Neueste Erkenntnisse zeigen, dass Zellen des Abwehrsystems bei der Sepsis im Rahmen der Immunantwort häufig eine Signalkaskade aktivieren, die zum programmierten Zelltod, der sog. Apoptose, führt. Apoptose von Leukozyten wurde sowohl im Tiermodell als auch bei Patienten mit Sepsis beobachtet. Bei der Regulation der Apoptose spielen das mitochondriale Protein Bcl-2 und die zytoplasmatische Enzymkaskade der Kaspasen eine wesentliche Rolle. Durch Überexprimierung von Bcl-2 oder Hemmung der Kaspasen konnte im Tiermodell der Sepsis ein deutlicher Überlebensvorteil demonstriert werden. Erste Arbeiten zeigten auch die Relevanz der Apoptose bei Patienten mit schwerer Sepsis. Ziel aktueller Forschung auf diesem Gebiet ist es, durch gezielte Beeinflussung der Apoptose neue molekulare Ansätze zur Therapie der Sepsis zu finden.

Abstract

Sepsis is still a leading cause of death in many intensive care patients. The pathophysiology of the disease is dominated by complex immune cascades. Recent research demonstrates that immune cells respond to sepsis with an increased rate of programmed cell death. Up-regulated apoptosis of leukocytes was observed in animal models of sepsis as well as in patients suffering from severe sepsis. The mitochondrial protein Bcl-2 and the caspase cascade play an important role in the regulation of apoptosis. Overexpression of Bcl-2 or inhibition of caspases resulted in an increased survival in animal models of sepsis. Recent reports indicate the relevance of apoptosis in patients with severe sepsis. These results may spawn novel immunomodulatory strategies in the treatment of sepsis.

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Authors and Affiliations

  1. Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Bonn, Rheinische Friedrich-Wilhems-Universität

    S. U. Weber, J.-C. Schewe, C. Putensen, F. Stüber & S. Schröder

  2. Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin, Rheinische Friedrich-Wilhems-Universität, Sigmund-Freud-Str. 25, 53105, Bonn

    S. U. Weber

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Weber, S.U., Schewe, JC., Putensen, C. et al. Apoptose als Pathomechanismus in der Sepsis. Anaesthesist 53, 59–65 (2004). https://doi.org/10.1007/s00101-003-0627-3

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