An endotoxin-induced serum factor that causes necrosis of tumors
E A Carswell, L J Old, R L Kassel, S Green, N Fiore, B Williamson, E A Carswell, L J Old, R L Kassel, S Green, N Fiore, B Williamson
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.
References
- J Exp Med. 1963 Sep 1;118:425-46
- Immunology. 1961 Oct;4:354-65
- J Natl Cancer Inst. 1952 Jun;12(6):1279-95
- Nat New Biol. 1971 Jul 21;232(29):76-8
- J Exp Med. 1973 Sep 1;138(3):625-44
- Harvey Lect. 1973;67:273-315
- Cell Immunol. 1973 Dec;9(3):339-52
- Br J Cancer. 1973 May;27(5):370-89
- Science. 1972 Sep 15;177(4053):998-1000
- Bacteriol Rev. 1969 Mar;33(1):72-98
- J Lab Clin Med. 1970 Jun;75(6):903-11
Source: PubMed