Acute Hemorrhagic Necrosis of Tumors Induced by Interleukin-1<IMG SRC="/math/alpha.gif" ALT="{alpha}" BORDER="0"> Effects Independent of Tumor Necrosis Factor

Tumor necrosis factor (TNF), a protein synthesized in response to the endotoxin bacterial lipopolysaccharide (LPS), is the classical mediator of acute hemorrhagic necrosis of tumors. We have demonstrated that interleukin-la (IL-lα), with a spectrum of activities very similar to those of TNF, also causes acute hemorrhagic necrosis of tumors. Both TNF and IL-1 induce a cascade of events including the synthesis or release of each other. The present studies were thus undertaken to determine whether the hemorrhagic necrosis induced in tumors by IL-lα is due to TNF. Kinetic parameters of IL-lα-induced hemorrhage were similar to those observed with recombinant murine TNF-α (TNF-α) or LPS in RIF-1 fibrosarcomas in C3H/HeN (endotoxin-sensitive) mice. However, the amount of TNF found in the sera or tumors of animals treated with LPS was more than 20-fold higher than in mice treated with IL-lα, and LPS induced similar degrees of hemorrhagic necrosis, which was measured by determining the packed volume of red blood cells by 59Fe labeling. A low but significantly hemorrhagic dose of IL-lα induced no detectable TNF in tumors. Pretreatment with 250 μg of neutralizing antibody to TNF had no effect on IL-lα-induced hemorrhage, whereas TNF-α- and LPS-induced hemorrhagic effects were significantly reduced. These results demonstrate an important antitumor activity of IL-αa that appears to be independent of TNF. [J Natl Cancer Inst 83:842–848,1991]