PMID- 7743604 OWN - NLM STAT- MEDLINE DCOM- 19950613 LR - 20061115 IS - 0092-6213 (Print) IS - 0092-6213 (Linking) VI - 44 IP - 2 DP - 1994 Oct TI - Potentiation of the toxicity of tumor necrosis factor by tumors in mice. PG - 77-83 AB - Tumor necrosis factor-alpha (TNF-alpha) was reported to be important in the induction of septic shock. After i.v. injection of recombinant TNF-alpha (rTNF-alpha), BALB/c mice bearing Meth A fibrosarcoma (Meth A), but not normal mice, died of shock. Tumor cells are known to release many biological components. In this study, we examined the role of the tumor in the toxicity of rTNF-alpha in mice. Meth A cells maintained i.p. in mice were cultured for 24 hr in vitro. Conditioned medium (CM) obtained from the Meth A cells was given i.v. to mice, and 2 to 7 days later, i.v. injection of rTNF-alpha induced death in the animals. rTNF-alpha treatment 4 days after Meth A CM gave the maximum effect. rTNF-alpha did not induce death in mice treated with CM from spleen cells. However, after the Meth A cells were passaged 2 or 3 times in in vitro culture, the CM did not potentiate the toxicity of rTNF-alpha in mice. rTNF-alpha induced symptoms of disseminated intravascular coagulation (DIC) on coagulation parameters in the blood, and high plasma tissue factor (TF) activity in Meth A CM-treated mice and Meth A tumor-bearing mice. These results suggest that factor(s) are released from tumor cells activated by interaction with host cells, and injection of rTNF-alpha and the factor(s) results in the induction of DIC syndrome leading to host death. FAU - Nishigaki, F AU - Nishigaki F AD - Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan. FAU - Miyayasu, K AU - Miyayasu K FAU - Tsujimoto, S AU - Tsujimoto S FAU - Manda, T AU - Manda T FAU - Shimomura, K AU - Shimomura K LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Circ Shock JT - Circulatory shock JID - 0414112 RN - 0 (Tumor Necrosis Factor-alpha) RN - 9035-58-9 (Thromboplastin) SB - IM MH - Animals MH - Female MH - Injections, Intravenous MH - Mice MH - Mice, Inbred BALB C MH - Neoplasms, Experimental/blood/*pathology MH - Thromboplastin/metabolism MH - Tumor Cells, Cultured/drug effects MH - Tumor Necrosis Factor-alpha/*toxicity EDAT- 1994/10/01 00:00 MHDA- 1994/10/01 00:01 CRDT- 1994/10/01 00:00 PHST- 1994/10/01 00:00 [pubmed] PHST- 1994/10/01 00:01 [medline] PHST- 1994/10/01 00:00 [entrez] PST - ppublish SO - Circ Shock. 1994 Oct;44(2):77-83.