Nonspecific macrophage activation by systemic adjuvants. Evaluation by lysosomal enzyme and in vitro tumoricidal activities

Abstract

Six systemic adjuvants: living bacillus Calmette-Guérin (BCG), hydrosoluble extracts from BCG and from Mycobacterium smegmatis, bacterial lipopolysaccharide, lentinan and levamisole, have been tested for their ability to induce macrophage activation in mice. The first four adjuvants mentioned increase phosphatase activity of peritoneal macrophages and make them nonspecifically cytotoxic for tumor cells in vitro. The intensity of these phenomena vary with route and time of administration. In contrast, lentinan and levamisole depress both these macrophage activities. Living BCG, extracts from BCG and from M. smegmatis, and the lipopolysaccharide increase the cytotoxic potential of normal macrophages in vitro, suggesting that these agents may exert a direct action on macrophages. Levamisole did not activate normal macrophages in vitro. The existence of a correlation between the capacity of adjuvants to stimulate macrophage tumoricidal activity and their efficiency in active cancer immunotherapy is discussed.