Zusammenfassung
Seit fast 40 Jahren beschäftigt sich die Forschung intensiv damit, die Pathophysiologie
der Sepsis besser zu verstehen und Ansätze für eine mögliche Behandlung zu definieren.
Mit Ausnahme von einer Form von aktiviertem Protein C (APC) scheiterten alle zuvor
durchgeführten Behandlungsversuche an septischen Patienten spätestens in den Phase-II-
und -III-Studien.
Die Behandlungsansätze umfassten dabei ein ungewöhnlich breites Spektrum. Trotz des
ersten Erfolges mit aktiviertem Protein C sind die immunologischen Veränderungen,
die zu den septischen Symptomen von Patienten führen, nur ungenügend gut verstanden.
Auch die Wirkweise von aktiviertem Protein C ist bislang nicht im Detail bekannt.
Allgemeine Übereinkunft herrscht darüber, dass gewisse komplexe Systeme (Komplementsystem,
Gerinnung, Akutphase-Proteine) sowie verschiedene proinflammatorische Schlüsselmediatoren
(z.B. HMGB-1, MIF, TNFα, IL-6, C5a und andere) für die Entwicklung der Sepsis eine
bedeutende Rolle spielen. Die Schwierigkeit liegt jedoch besonders darin, die Interaktion
dieser Systeme, Zytokine und Proteine zu verstehen. Der folgende Artikel beschäftigt
sich kritisch mit ausgewählten neuen Aspekten der Pathophysiologie im Anfangsstadium
der Sepsis und beschreibt mögliche neue Behandlungsansätze und deren Hintergrund.
Summary
For more than thirty years now, there have been attempts to treat sepsis with various
different strategies, most of them pursuing anti-inflammatory concepts. Ever since,
researchers have been struggling to obtain a better understanding of the pathophysiology
of sepsis. With exception of a recombinant form of activated protein C (APC) all other
clinical trials have failed to demonstrate significant benefits in larger phase II
and III trials. Despite the first success with activated protein C, research is far
from understanding the immunological changes leading to the clinical symptoms of sepsis,
and even the mechanism by which activated protein C provides beneficial effects is
not known so far. There is general agreement that various complex systems (complement
system, coagulation, acute phase serum proteins) and certain key mediators (e.g. HMGB-1,
MIF, IL-6, TNFα, C5a and others) play an important role for the onset of sepsis. It
appears to be particularly difficult to understand how these complex systems and mediators
interact and influence each other. The following article critically discusses selected
aspects of pathophysiological changes during the onset of sepsis and describes emerging
potential targets for the treatment of sepsis.
Key Words
sepsis - C5a-MIF-apoptosis - antiinflammation - activated protein C - complement system
- coagulation - HMGB1
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1 acute physiology and chronic health evaluation
Anschrift für die Verfasser
Dr. Niels Christoph Riedemann
Unfallchirurgische Klinik, Medizinische Hochschule Hannover
Carl-Neuberg-Str. 1
30625 Hannover
