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.
Kobayashi
Kohji
K
Medical Research Laboratory, Sekisui Chemical Co. Ltd., 2-1 Hyakuyama, Mishima-gun, Osaka 618-8589, Japan. kobayashi039@sekisui.jp
Abe
Yoshiko
Y
Kuriyama
Kiyoshi
K
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D005472:Fluorouracil / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002945:Cisplatin; D005472:Fluorouracil