Whole blood TNF-alpha production as a sensitive measure for immunotoxicity of anticancer drugs

The immunotoxicity of anticancer drugs has been measured with whole blood TNF-alpha production induced by LPS-stimulation. Cis-platinum (CDDP) or 5-fluorouracil (5-FU) was given intravenously to mice once a day for three days. The amount of produced-TNF-alpha lowered significantly in CDDP 2 mg/kg and 5 mg/kg, while the number of leukocytes scarcely changed even when a significant decrease in body weight was observed at the dose of 5 mg/kg. On the other hand, 5-FU 20 mg/kg also caused a significant decline in the amount of produced TNF-alpha but it showed no apparent effects on the number of leukocytes and the body weight. These results indicate that LPS-induced TNF-alpha production is a more sensitive measure than leukocyte count used conventionally to detect the immunotoxicity of two anticancer drugs, CDDP and 5-FU, and suggest that it might be a more practical index for hazard identification in clinical treatment with anticancer drugs.