Von der Katabolie zur Anabolie: Stoffwechselmediatoren und Therapieansätze

 

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Zusammenfassung

Der Gesamtkörper-Proteinkatabolismus ist bei Tumorkachexie in Relation zum Energieverbrauch oft erhöht; eine Steigerung des Energieverbrauchs wird in ca. ⅓ aller Tumorpatienten gefunden und verstärkt den Protein-Katabolismus. Vom Wirt produzierte Mediatoren wie TNF-α, IL-6, NFκB, PIF und Eicosanoide spielen eine Rolle beim Proteinkatabolismus. Sie werden u. a. von Makrophagen durch Tumorsignale, die weitgehend ungeklärt sind, gebildet. Glukokortikoide sind zwar wirksam als Appetitstimulanzien; sie sind jedoch protein-katabol. Das Gestagen Megestrol ist appetitstimulierend, fett-anabol, erhöht aber nicht die Muskelmasse. Für Wachstumshormon (GH) und IGF-1 existieren keine kontrollierten Studien bei Tumorpatienten. GH erhöhte bei Schwerkranken die Mortalität. Fischöle sind interessant, da eine direkte protein-antikatabole Wirkung gezeigt wurde; es fehlen aber auch hier kontrollierte Studien.

From Catabolism to Anabolism: Metabolic Mediators and Therapeutic Strategies

Tumour cachexia is characterised by protein catabolism and by a relative decrease in protein synthesis. Resting energy is not generally altered - in approximately ⅓ of cancer patients it is increased. In this case it contributes to protein catabolism when nutritional intake is inadequate. Mediators such as cytokines (TNF-α, IL-6, NFκB, PIF and eicosanoids) are produced by the host (e.g. by macrophages) upon poorly understood signals released by tumor cells. Glucocorticoids are used as stimulants of appetite, however, their potent protein-catabolic effect limits their usefulness. The gestagen megestrol is also recognized to stimulate appetite; it has been shown to increase fat mass, without increasing muscle mass. Growth hormone (GH) and IGF-1 have not been tested in tumour cachexia, however, two recent studies in critically ill patients showed a higher mortality with GH than with placebo. Fish oils (EPA, DHA) are of interest since direct anti-protein-catabolic effects have been show in vitro. Again, clinical trials with „hard” clinical endpoints are missing.

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Prof. Ulrich Keller

Abteilung für Endokrinologie, Diabetologie & Klin. Ernährung
Medizinische Universitätsklinik
Kantonsspital Basel

4031 Basel
Schweiz

Email: ukeller@uhbs.ch