Glucocorticoid-mediated inhibition of endotoxin-induced intratumor tumor necrosis factor production and tumor hemorrhagic necrosis and regression

Intravenous injection of 25 micrograms of bacterial endotoxin on day 9 of growth of the SA1 sarcoma results in extensive necrosis of the core of this tumor and in its subsequent complete regression. Tumor hemorrhagic necrosis and regression failed to occur in mice that were given a subcutaneous injection of cortisone acetate or dexamethasone 12 h before being giving endotoxin. Inhibition of tumor hemorrhagic necrosis and regression by glucocorticoids was associated with inhibition of endotoxin-induced intratumor TNF production that normally takes place several h after endotoxin is given. In contrast, glucocorticoids had no effect on the ability of intravenously injected rTNF to cause tumor hemorrhagic necrosis and regression. The results lend further support to the belief that TNF is the predominant mediator of endotoxin-induced hemorrhagic necrosis of established murine tumors, and that hemorrhagic necrosis is a prerequisite for the immunologically mediated regression that follows.