Release of tumor necrosis factor (TNF) into mouse peritoneal fluids by OK-432, a streptococcal preparation.

A cytotoxic factor was induced in peritoneal fluid by injection of OK-432 in mice which had been primed with OK-432. Two-step stimulation (priming and eliciting) was always necessary to induce the cytotoxic factor. OK-432-primed mice did not produce soluble cytotoxic factor spontaneously and no cytotoxic activity was detected in the mice treated by a single injection of OK-432 as an eliciting agent. This observation was also confirmed by in vitro experiments. Only when activated macrophages were incubated with OK-432 (or with lipopolysaccharide) was cytotoxin released into medium supernatant. High doses of OK-432 were required to prime mice for the production of cytotoxic factor, whereas a small amount was enough to elicit. The peritoneal cytotoxic factor obtained by OK-432 injection appears to be identical to tumor necrosis factor in the serum for the following reasons: The two factors are similar in mode of cytotoxic action. Both are produced from macrophages. They are similar in physicochemical characteristics. The cytotoxicity of the peritoneal cytotoxic factor was totally abolished by anti-TNF serum.