Studies on thermophile products. VI. Activation of mouse peritoneal macrophages by bis(2-hydroxyethyl) trisulfide

The biological effects of a cytotoxic substance (BS-1), isolated from Bacillus stearothermophilus UK563 and identified as bis(2-hydroxyethyl) trisulfide, on elicited mouse peritoneal macrophages induced by a casein injection, were investigated in vitro. BALB/c mouse macrophages treated or pretreated with BS-1 (1-10 micrograms/ml) showed cytotoxicity against syngeneic DBA/2 mouse P815 mastocytoma. BS-1 also showed weak cytotoxicity directly against P815 in the absence of macrophages. BS-1 significantly increased the glucose consumption of macrophages without producing cytotoxicity. This trisulfide compound increased nitric oxide formation, interleukin-1 production and prostaglandin E2 release in macrophages. It did not, however, increase the production of active oxygen species in macrophages, but it reduced cytochrome c in the presence of phagocytes. These results indicate that BS-1 activates macrophages to the cytolytic stage.