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. 1975 Sep;72(9):3666-70.
doi: 10.1073/pnas.72.9.3666.

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

An endotoxin-induced serum factor that causes necrosis of tumors

E A Carswell et al. Proc Natl Acad Sci U S A. 1975 Sep.

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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