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Proc Natl Acad Sci U S A. Sep 1975; 72(9): 3666–3670.
PMCID: PMC433057

An endotoxin-induced serum factor that causes necrosis of tumors.

Abstract

In studying "hemorrhagic necrosis" of tumors produced by endotoxin, it was found that the serum of bacillus Calmette--Guerin (BCG)-infected mice treated with endotoxin contains a substance (tumor necrosis factor; TNF) which mimics the tumor necrotic action of endotoxin itself. TNF-positive serum is as effective as endotoxin itself in causing necrosis of the sarcoma Meth A and other transplanted tumors. A variety of tests indicate that TNF is not residual endotoxin, but a factor released from host cells, probably macrophages, by endotoxin. Corynebacteria and Zymosan, which like BCG induce hyperplasia of the reticulo-endothelial system, can substitute for BCG in priming mice for release of TNF by endotoxin. TNF is toxic in vitro for two neoplastic cell lines; it is not toxic for mouse embryo cultures. We propose that TNF mediates endotoxin-induced tumor necrosis, and that it may be responsible for the suppression of transformed cells by activated macrophages.

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Selected References

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  • Old LJ, Boyse EA. Current enigmas in cancer research. Harvey Lect. 1973;67:273–315. [PubMed]
  • Nowotny A. Molecular aspects of endotoxic reactions. Bacteriol Rev. 1969 Mar;33(1):72–98. [PMC free article] [PubMed]
  • Parr I, Wheeler E, Alexander P. Similarities of the anti-tumour actions of endotoxin, lipid A and double-stranded RNA. Br J Cancer. 1973 May;27(5):370–389. [PMC free article] [PubMed]
  • SUTER E, KIRSANOW EM. Hyperreactivity to endotoxin in mice infected with mycobacteria. Induction and elicitation of the reactions. Immunology. 1961 Oct;4:354–365. [PMC free article] [PubMed]
  • WATSON DW, KIM YB. MODIFICATION OF HOST RESPONSES TO BACTERIAL ENDOTOXINS. I. SPECIFICITY OF PYROGENIC TOLERANCE AND THE ROLE OF HYPERSENSITIVITY IN PYROGENICITY, LETHALITY, AND SKIN REACTIVITY. J Exp Med. 1963 Sep 1;118:425–446. [PMC free article] [PubMed]
  • Levin J, Tomasulo PA, Oser RS. Detection of endotoxin in human blood and demonstration of an inhibitor. J Lab Clin Med. 1970 Jun;75(6):903–911. [PubMed]
  • ALGIRE GH, LEGALLAIS FY, ANDERSON BF. Vascular reactions of normal and malignant tissues in vivo. V. The rôle of hypotension in the action of a bacterial polysaccharide on tumors. J Natl Cancer Inst. 1952 Jun;12(6):1279–1295. [PubMed]
  • Alexander P, Evans R. Endotoxin and double stranded RNA render macrophages cytotoxic. Nat New Biol. 1971 Jul 21;232(29):76–78. [PubMed]
  • Hibbs JB, Jr, Lambert LH, Jr, Remington JS. Control of carcinogenesis: a possible role for the activated macrophage. Science. 1972 Sep 15;177(4053):998–1000. [PubMed]
  • Keller R. Cytostatic elimination of syngeneic rat tumor cells in vitro by nonspecifically activated macrophages. J Exp Med. 1973 Sep 1;138(3):625–644. [PMC free article] [PubMed]
  • Holtermann OA, Klein E, Casale GP. Selective cytotoxicity of peritoneal leucocytes for neoplastic cells. Cell Immunol. 1973 Dec;9(3):339–352. [PubMed]

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