Similarities among factors that render macrophages tumoricidal in lymphokine and interferon preparations

Abstract

Lymphokine preparations, including supernatants derived from antigen-stimulated Bacillus Calmette-Guérin-immune spleen cell cultures and normal spleen cells incubated with insoluble concanavalin A, were compared with partially purified L-cell interferon for the ability to render resting macrophages nonspecifically tumoricidal in vitro. Significant activation of macrophages by lymphokine preparations occurred at concentrations as low as 0.5 and 0.25% of the assay mixture for antigen-stimulated and concanavalin A-induced lymphokine, respectively. These end point concentrations were each determined to contain 0.3 unit of interferon per ml. Supernatants obtained from unstimulated normal spleen cells, concanavalin A-treated nu/nu spleen cells, or Bacillus Calmette-Guérin-immune spleen cells in the absence of sensitizing antigen did not enhance macrophage tumoricidal function and lacked interferon. Activation by L-cell interferon required at least 1 unit/ml. The macrophage-activating factors contained in lymphokine and interferon preparations were stable at pH 2 and at 56 degrees, but they were destroyed when heated at 80 degrees for 30 min, and were inactivated by trypsin. The data demonstrate common properties for the induction of tumoricidal macrophages by these divese preparations.