title: Acute hemorrhagic necrosis of tumors induced by interleukin-1 alpha: effects independent of tumor necrosis factor.
abstract: 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-1 alpha (IL-1 alpha), 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-1 alpha is due to TNF. Kinetic parameters of IL-1 alpha-induced hemorrhage were similar to those observed with recombinant murine TNF-alpha (TNF-alpha) 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-1 alpha, 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-1 alpha induced no detectable TNF in tumors. Pretreatment with 250 micrograms of neutralizing antibody to TNF had no effect on IL-1 alpha-induced hemorrhage, whereas TNF-alpha- and LPS-induced hemorrhagic effects were significantly reduced. These results demonstrate an important antitumor activity of IL-1 alpha that appears to be independent of TNF.
authors.affiliation: Department of Otolaryngology, University of Pittsburgh, School of Medicine, Pa 15213.
authors.forename: C S
authors.initials: CS
authors.lastname: Johnson
authors.forename: M J
authors.initials: MJ
authors.lastname: Chang
authors.forename: P G
authors.initials: PG
authors.lastname: Braunschweiger
authors.forename: P
authors.initials: P
authors.lastname: Furmanski
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006470:Hemorrhage / Q000139:chemically induced*; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009336:Necrosis; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology* / Q000633:toxicity
chemical_list: D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha