Endogenous production of tumor necrosis factor alpha in combination with hyperthermia for the treatment of mice bearing Ehrlich ascites tumor.

Multiple hyperthermia was found to exert an additive antitumor effect when combined with the in vivo production of tumor necrosis factor alpha (TNF-alpha) in mice bearing Ehrlich ascites tumor (EAT). TNF-alpha was produced in EAT-bearing mice by priming the animals with zymosan and subsequently challenging with lipopolysaccharide (LPS). Mice were pretreated with sulindac and D-mannoheptulose to alleviate the toxic side effects of LPS. While the ability of these tumor-bearing mice to produce TNF-alpha remained unchanged under hyperthermia, the EAT cell number was suppressed in the combined-treatment group compared with groups treated with TNF-alpha or hyperthermia alone. In the same comparison, the life span of EAT-bearing mice in the combined-treatment group was prolonged.