Effect of Recombinant Human Tumor Necrosis Factor on the Induction of Murine Macrophage Tumoricidal Activity1

The ability of recombinant human tumor necrosis factor (rH-TNF) alone or in combination with lymphokines (LK) to induce the in vitro activation of murine macrophages was evaluated. The treatment of C57BL/6 mouse resident peritoneal exÃodatecells (PEC) with rH-TNF and LK was found to induce the activation of macrophages to a tumoricidal state against P815 mastocytoma cells. Neither rH-TNF nor LK alone induced macrophage cytotoxic activity. Furthermore, the macro phage activation seen was not due to small amounts of contaminating lipopolysaccharide. The IM plus LK-mediated macrophage activation could be totally ablated by rabbit antiserum to murine •Y-interferon, thus suggesting a role for 7-interfcroti in this system. Since adherent cells (>95% macrophages) only marginally responded to stimulation with rHTNF plus LK and the addition of nonadherent PEC caused a marked augmentation of rH-TNF plus UK-mediated macrophage activation, the involvement of nonadherent PEC was suggested. In addition, using anti bodies and complement to deplete subsets of cells from the nonadherent PEC, the requirement for cells bearing Thy 1.2 and asialo GMI surface markers was demonstrated. These results suggest that TNI may play an autocrine regulatory role in concert with lymphokines in macrophagemediated host defense against malignant neoplasia.