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Die Bedeutung der Zytokine in der posttraumatischen Entzündungsreaktion

The importance of cytokines in the posttraumatic inflammatory reaction

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Zusammenfassung

Veränderungen der Immunantwort nach Polytrauma, posttraumatischer Sepsis und operativen Eingriffen stellen eine physiologische Reaktion des Organismus zur Aufrechterhaltung der Homöostase dar. Das Ausmaß dieser immunologischen Reaktionen korreliert dabei mit der Schwere des Gewebeschadens sowie dem Ausmaß der Hämorrhagie und Ischämie. Zytokine werden als integraler Bestandteil der Immunantwort angesehen.

Die lokale Freisetzung von pro- und antiinflammatorischen Zytokinen nach Polytrauma kann systemische Organreaktionen beeinflussen und damit den klinischen Verlauf maßgeblich beeinträchtigen. Bei einem Überwiegen der proinflammatorischen Zytokine kommt es zu einer systemischen Entzündungsreaktion („systemic inflammatory response syndrome“, SIRS), wohingegen eine Überproduktion antiinflammatorischer Mediatoren in einer Immunsuppression mit einem erhöhten Risiko infektiologischer Komplikationen resultieren kann. Sowohl das SIRS als auch die Immunsuppression scheinen bei der Entwicklung eines „Multiorgandysfunktionssyndroms“ (MODS) eine signifikante Rolle zu spielen.

Tumornekrosefaktor-α (TNF-α), Interleukin–1β (IL-1β), Interleukin-6 (IL-6) and Interleukin-8 (IL-8) stellen die wesentlichen proinflammatorischen Zytokine für den posttraumatischen Verlauf dar. Diese Zytokine vermitteln eine Vielzahl von teilweise auch üperlappenden und additiven Effekten. TNF-α and IL-1β sind frühe Regulatoren der Immunantwort, und beide können die Freisetzung sekundärer Zytokine, wie IL-6 und IL-8 induzieren. Interleukin-10 (IL-10) ist ein antiinflammatorisches Zytokin, das die Synthese proinflammatorischer Mediatoren reduziert. Andere wichtige antiinflammatorische Mediatoren sind lösliche TNF-Rezeptoren (TNF-RI und -RII) und der IL-1-Rezeptorantagonist (IL-1ra), die mit den Wirkungen des TNF-α and IL-1β interferieren.

Die frühe Einschätzung der Prognose und des klinischen Zustands der polytraumatisierten Patienten stellt sich als äußerst schwierig dar. In einer Vielzahl von Studien sind daher Zytokinkonzentrationen im posttraumatischen Verlauf bestimmt worden, um prognostische Marker für das Outcome der Patienten zu identifizieren. Des Weiteren wurden ebenso systemische Zytokinspiegel bestimmt, um den günstigsten Zeitpunkt für den chirurgischen Eingriff nach einem Polytrauma festzulegen und das Ausmaß des Eingriffs zu quantifizieren. Das Ziel dieser Arbeit ist es, den aktuellen Wissensstand bezüglich der Assoziation zwischen posttraumatischen Zytokinsynthese und der Entwicklung von Komplikationen zusammenzufassen. Ein verbessertes Verständnis dieser Mechanismen könnte zur Erstellung neuer diagnostischer und therapeutischer Behandlungsstrategien im klinischen Alltag beitragen.

Abstract

Alterations in the immune response after multiple trauma, posttraumatic sepsis and surgery are recognized as physiological reactions of the organism to restore homeostasis. The level of these immunological changes correlates with the degree of tissue damage as well as with the severity of haemorrhage and ischaemia. Cytokines are known to be integral components of this immune response.

The local release of pro- and antiinflammatory cytokines after severe trauma indicates their potential to induce systemic immunological alterations. It appears that the balance or imbalance of these different cytokines partly controls the clinical course in these patients. Overproduction of either proinflammatory cytokines or antiinflammatory mediators may result in organ dysfunction. Whereas predominance of the proinflammatory response leads to the systemic inflammatory response syndrome (SIRS), the antiinflammatory reaction may result in immune suppression with an enhanced risk of infectious complications. Systemic inflammation, as well as immune suppression, are thought to play a decisive role in the development of multiple organ dysfunction syndrome (MODS).

The major proinflammatory cytokines involved in the response to trauma and surgery include tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-8. These cytokines, which are predominantly produced by monocytes and macrophages, mediate a variety of frequently overlapping effects, and their actions can be additive. TNF-α and IL-1β are early regulators of the immune response and both induce the release of secondary cytokines, such as IL-6 and IL-8. IL-10 is an antiinflammatory cytokine which reduces the synthesis of proinflammatory mediators. Other important antiinflammatory mediators are soluble TNF receptors and the IL-1 receptor antagonist, which interfere with the effects of TNF-α and IL-1β.

Early evaluation of the prognosis of polytraumatized patients and assessment of their clinical status is known to be difficult. Therefore, in several clinical studies, cytokine levels during the posttraumatic course have been determined with the aim of finding predictive markers of patient outcome. The purpose of this review was to highlight our current knowledge on the interaction of posttraumatic immune reactivity and the development of complications. A better understanding of these mechanisms might lead to the introduction of preventive and therapeutic strategies into clinical practice.

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  1. Unfallchirurgische Klinik, Medizinische Hochschule Hannover

    F. Hildebrand, H.-C. Pape & C. Krettek

  2. Unfallchirurgische Klinik, Medizinische Hochschule Hannover, Carl-Neuberg-Straße 1, 30625 , Hannover

    F. Hildebrand

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  1. F. Hildebrand
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  2. H.-C. Pape
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  3. C. Krettek
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Correspondence to F. Hildebrand.

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Hildebrand, F., Pape, HC. & Krettek, C. Die Bedeutung der Zytokine in der posttraumatischen Entzündungsreaktion. Unfallchirurg 108, 793–803 (2005). https://doi.org/10.1007/s00113-005-1005-1

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