Veränderungen des Zytokin-Netzwerkes bei eskalierendem SIRS nach herzchirurgischen Operationen[*]

Zusammenfassung.

Die Anwendung der extrakorporalen Zirkulation (EKZ) im Rahmen kardiochirurgischer Operationen führt zu einer ausgeprägten inflammatorischen Reaktion, die jedoch nur bei einem geringen Anteil der betroffenen Patienten zu klinischen Komplikationen und einer erhöhten Letalität führt („eskalierendes SIRS”). In der gegenwärtigen Literatur gibt es nur wenige und unzureichende Angaben über Veränderungen des Immunsystems bei Patienten, die in der frühen postoperativen Phase ein schweres SIRS mit begleitenden Organinsuffizienzen entwickeln. In der vorliegenden Studie wird untersucht, in welchem Ausmaß das eskalierende SIRS in der frühen Phase nach kardiochirurgischen Operationen zu Veränderungen des Zytokin-Netzwerkes führt und ob sich die Expression von Zytokinen bei Überlebenden und Verstorbenen unterscheidet. Dazu untersuchten wir die Serumspiegel der Zytokine IL-1β, IL-6, IL-8, IL-10, IL-12, IL-18, GM-CSF und TGF-β bei 12 Patienten mit eskalierendem SIRS (SIRS-Gruppe) und 15 Patienten mit unauffälligem Verlauf (Kontroll-Gruppe) an den ersten 4 postoperativen Tagen nach elektiver Myokardrevaskularisierung. Die in der Literatur dargestellten Veränderungen von Mediatoren des Immunsystems nach herzchirurgischen Eingriffen können anhand der Ergebnisse bestätigt werden, darüber hinaus findet sich bei eskalierendem SIRS eine bisher noch nicht beschriebene Zunahme der Immun-Dysregulation: Sowohl die Serumspiegel der pro-inflammtorischen Zytokine IL-6, IL-8, IL-18 und GM-CSF, als auch die der immun-inhibierenden Zytokine IL-10 und TGF-beta sind bei den Patienten mit schwerem SIRS signifikant erhöht. Eine nochmalige Zunahme der Expression von IL-8 und IL-18 zeigt sich bei den verstorbenen Patienten der SIRS-Gruppe. Das eskalierende SIRS nach herzchirurgischen Operationen stellt somit ein uneinheitliches immunologisches Geschehen dar, welches sowohl pro- als auch anti-inflammatorische Komponenten beinhaltet. Die Zytokine IL-8 und IL-18 scheinen hierbei bereits zu einem frühen Zeitpunkt die Diskriminierung von Hochrisikopatienten zu ermöglichen.

Changes in the Cytokine Network Through Escalating SIRS After Heart Surgery.

Cardiopulmonary bypass is associated with an injury that may cause pathophysiological changes in form of systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS). There is a lot of information about the immunologic alterations in patients undergoing cardiopulmonary bypass, but only little is known about the expression of cytokines in patients with severe SIRS or MODS following cardiovascular surgery. In the present study, we investigated the inflammatory response of patients with an escalating SIRS following open heart surgery. Plasma levels of cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12, IL-18, GM-CSF and TGF-β) were measured at the first four postoperative days in 12 adult male patients with severe SIRS (SIRS-group), and 15 patients with uncomplicated course (control-group) following myocardial revascularization. All cytokines (except IL-1β) were significantly elevated in SIRS-patients, the analysis of differences between the survivors and non-survivors within the SIRS-group showed dramatically elevated levels of IL-8 and IL-18 in non-survivors. From the results of our investigation we can conclude that monitoring of immunologic parameters, e.g. IL-8 and/or IL-18 may be helpful for the early detection and prognosis of high-risk patients with severe SIRS and MODS following cardiac surgery.

Interleukine - SIRS - MODS - EKZ

Interleukins - Severe SIRS - MODS - Cardiopulmonary bypass

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1 Herrn Prof. Dr. med. D. Kettler und Herrn Prof. Dr. med. H. Sonntag zum 65. Geburtstag gewidmet.