Von der Katabolie zur Anabolie: Stoffwechselmediatoren und Therapieansätze

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.

Literatur

• 1 Dewys W D, Begg C, Lavin P l. et al . Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group.  Am J Med. 1980;  69 491-497
• 2 Knox L S, Crosby L O, Feurer I D, Buzby G P, Miller C L, Mullen J L. Energy expenditure in malnourished cancer patients.  Ann Surg. 1983;  197 152-162
• 3 Wilmore D W. Catabolic illness. Strategies for enhancing recovery.  N Engl J Med. 1991;  325 695-702
• 4 Kern K A, Norton J A. Cancer cachexia.  JPEN J Parenter Enteral Nutr. 1988;  12 286-298
• 5 Rutanen E M, Karkkainen T, Stenman U H, Yki Jarvinen H. Aging is associated with decreased suppression of insulin-like growth factor binding protein-1 by insulin.  J Clin Endocrinol Metab. 1993;  77 1152-1155
• 6 Lee E G, Boone D L, Chai S. et al . Failure to regulate TNF-induced NF-κB and cell death responses in A20-deficient mice.  Science. 2000;  289 2350 2354
• 7 Tisdale M J. Biomedicine. Protein loss in cancer cachexia.  Science. 2000;  289 2293-2294
• 8  Federation of the French Cancer Centres (FNCLCC). Standards, Options and Recommendations (SOR) for the use of appetite stimulants in oncology. Work group.  Bull Cancer. 2000;  87 315-328
• 9 Oehri M, Ninnis R, Girard J, Frey F J, Keller U. Effects of growth hormone and IGF-I on glucocorticoid-induced protein catabolism in humans.  Am J Physiol. 1996;  270 E552-558
• 10 Takala J, Ruokonen E, Webster N R. et al . Increased mortality associated with growth hormone treatment in critically ill adults (see comments).  N Engl J Med. 1999;  341 785-792
• 11 Wigmore S J, Barber M D, Ross J A, Tisdale M J, Fearon K C. Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic cancer.  Nutr Cancer. 2000;  36 177-184
• 12 Stratton R J, Elia M. The effects of enteral tube feeding and parenteral nutrition on appetite sensations and food intake in health and disease.  Clin Nutr. 1999;  18 63-70