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

TLDR

The study proposes that tumor necrosis factor mediates endotoxin‑induced tumor necrosis and may suppress transformed cells via activated macrophages. The authors demonstrate that priming mice with BCG‑like agents such as Corynebacteria or Zymosan induces reticulo‑endothelial hyperplasia that primes endotoxin to release TNF. Serum TNF from BCG‑infected, endotoxin‑treated mice induces hemorrhagic tumor necrosis comparable to endotoxin, originates from host macrophages, and is selectively toxic to neoplastic cells but not to embryonic cultures.

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.