An endotoxin-induced serum factor that causes necrosis of tumors (activated macrophage)

An endotoxin-induced serum factor that causes necrosis of tumors (activated macrophage)

September 1975 | E. A. CARSWELL, L. J. OLD, R. L. KASSEL, S. GREEN, N. FIORE, AND B. WILLIAMSON
The study by Carswell et al. (1975) identified a serum factor, tumor necrosis factor (TNF), produced in mice infected with BCG and treated with endotoxin. This factor mimics the tumor necrotic effect of endotoxin itself, causing necrosis of transplanted tumors like Meth A. TNF is not residual endotoxin but a factor released from host cells, likely macrophages. Corynebacteria, Zymosan, and mixed bacterial vaccine can also prime mice for TNF release. TNF is toxic to certain neoplastic cell lines in vitro but not to mouse embryo cultures. The study suggests that TNF mediates endotoxin-induced tumor necrosis and may explain the suppression of transformed cells by activated macrophages. TNF is a glycoprotein with a molecular weight of about 150,000, which does not contain the sugar KDO or the fatty acid characteristic of endotoxin. The cellular origin of TNF is uncertain, but macrophage-inciting agents are necessary for its demonstration in serum. The study also shows that TNF is produced by various mouse strains and other mammals like rats and rabbits. TNF's activity against cultured cells is consistent with its in vivo effects. The study highlights the role of TNF in tumor necrosis and its potential as a therapeutic target.The study by Carswell et al. (1975) identified a serum factor, tumor necrosis factor (TNF), produced in mice infected with BCG and treated with endotoxin. This factor mimics the tumor necrotic effect of endotoxin itself, causing necrosis of transplanted tumors like Meth A. TNF is not residual endotoxin but a factor released from host cells, likely macrophages. Corynebacteria, Zymosan, and mixed bacterial vaccine can also prime mice for TNF release. TNF is toxic to certain neoplastic cell lines in vitro but not to mouse embryo cultures. The study suggests that TNF mediates endotoxin-induced tumor necrosis and may explain the suppression of transformed cells by activated macrophages. TNF is a glycoprotein with a molecular weight of about 150,000, which does not contain the sugar KDO or the fatty acid characteristic of endotoxin. The cellular origin of TNF is uncertain, but macrophage-inciting agents are necessary for its demonstration in serum. The study also shows that TNF is produced by various mouse strains and other mammals like rats and rabbits. TNF's activity against cultured cells is consistent with its in vivo effects. The study highlights the role of TNF in tumor necrosis and its potential as a therapeutic target.
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