Abstract • Cachectin/tumor necrosis factor has been postulated to be a possible mediator of cancer cachexia. Using a sensitive bioassay, we attempted to detect circulating cachectin activity in the serum of sarcoma-bearing rats and to correlate levels with measurements of cachexia and the extent of disease. In addition, we resected the tumor to determine the time course of reversal of cachexia and the disappearance of cachectin activity in the serum. Circulating cachectin activity was not detectable in the serum of non–tumor-bearing rats or in tumorbearing rats until 28 days after implantation. With evidence of food intake and body weight decline, cachectin activity became detectable in the serum and levels increased as cachexia and tumor burden increased. Serum cachectin activity levels correlated directly with tumor burden and inversely with food intake and body weight change. After resection of the tumor, food intake and body weight increased and serum cachectin activity became undetectable. Serum triglyceride levels were higher in cachectic tumor-bearing rats than in pair-fed non–tumor-bearing controls, and levels decreased after tumor resection as cachectin activity decreased. The results suggest that cachectin is a humoral mediator of cachexia in this rattumor model. (Arch Surg 1989;124:94-99) References 1. Norton JA, Peacock JL, Morrison SD: Cancer cachexia . CRC Crit Rev Oncol Hematol 1987;7:289-327.Crossref 2. Theologides A: Pathogenesis of cachexia in cancer: A review and a hypothesis . Cancer 1972;20:484-488.Crossref 3. Norton JA, Moley JF, Green MV, et al: Parabiotic transfer of cancer anorexia/cachexia in male rats . Cancer Res 1985;45:5547-5552. 4. Beutler B, Cerami A: Cachectin and tumor necrosis factor as two sides of the same biological coin . Nature 1986;320:584-588.Crossref 5. Rouser CA, Cerami A: Hypertriglyceridemia associated with Trypanosoma brucei infection in rabbits: Role of defective triglyceride removal . Mol Biochem Parasitol 1980;2:31-38.Crossref 6. Tracey KJ, Beutler B, Lowry SF, et al: Shock and tissue injury induced by recombinant human cachectin . Science 1986;234:470-474.Crossref 7. Scuderi P, Sterling KE, Lam KS, et al: Raised serum levels of tumor necrosis factor in parasitic infections . Lancet 1986;2:1364-1365.Crossref 8. Waage A, Espivik T, Lamvik J: Detection of tumor necrosis factor like cytotoxicity in serum from patients with septicemia but not from untreated cancer patients . Scand J Immunol 1986;24:739-743.Crossref 9. Balkwill F, Burke F, Talbot D, et al: Evidence for tumor necrosis factor/cachectin production in cancer . Lancet 1987;2:1229-1232.Crossref 10. Peacock JL, Gorschboth CM, Norton JA: Impact of insulin on doxorubicin-induced rat host toxicity and tumor regression . Cancer Res 1987;47:4318-4322. 11. Popp MB, Morrison SD, Brennan MF: Total parenteral nutrition in a methylcholanthrene induced rat sarcoma model . Cancer Treat Rep 1981;65:137-143. 12. Flick DA, Gifford GE: Comparison of in vitro cell cytotoxic assays for tumor necrosis factor . J Immunol Methods 1984;68:167-175.Crossref 13. Beutler BJ, Mahoney N, LeTrang P, et al: Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells . J Exp Med 1985;161:984-995.Crossref 14. Cerami A, Beutler B: The role of cachectin/TNF in endotoxic shock and cachexia . Immunol Today 1988;9:28-31.Crossref 15. Kawakami M, Pekela PH, Lane MD, et al: Lipoprotein lipase suppression in 3T3-LI cells by an endotoxin-induced mediator from exudate cells . Proc Natl Acad Sci USA 1982;79:912-916.Crossref 16. Carswell EA, Old LS, Casse RL, et al: An endotoxin-induced serum factor that causes necrosis of tumors . Proc Natl Acad Sci USA 1975;72:3666-3670.Crossref 17. Aderka D, Fisher S, Levo Y, et al: Cachectin/tumor necrosis factor production by cancer patients . Lancet 1985;2:1190.Crossref 18. Stovroff MD, Norton JA: Cachectin: A mediator of cancer cachexia . Surg Forum 1987;38:413-415. 19. Oliff A, Defeo-Jones D, Boyer M, et al: Tumors secreting human TNF/cachectin induce cachexia in mice . Cell 1987;50:555-563.Crossref
Archives of Surgery – American Medical Association
Published: Jan 1, 1989
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