SOME REQUIREMENTS FOR THE SECRETION OF TUMOR-NECROSIS-FACTOR AND ITS CYTOTOXIC ACTIVITY INVITRO

The bacterial lipopolysaccharide (LPS) in vitro-induced secretion of tumour necrosis factor (TNF) by mouse macrophages is described. The highest amount of TNF was produced by DBA/2 mouse peritoneal macrophages activated by a dose of 1-mu-g LPS for 3 h. The yield of TNF was higher in the presence of indomethacin during LPS induction. A markedly positive effect on TNF yield of the priming of macrophages in vivo was manifested by proliferation of peritoneal macrophages and increased secretion of TNF as well. No significant effect of hyperthermia (41-degrees-C) on TNF secretion could be found. At 41-degrees-C, however, TNF cytotoxic activity against the tumour L-929 mouse cells was considerably increased and accelerated, even in the absence of actinomycin D. The maximum cytotoxic activity with or without actinomycin D was reached 15 h later, and it significantly exceeded the value obtained at 37-degrees-C at 20 h in the presence of actinomycin D; in the absence of the latter the maximum cytotoxic activity was reached in more than 48 h at 37-degrees-C.