Macrophages by Interleukin 2 and Tumor Necrosis Factor Tumoricidal Activation of Murine Resident Peritoneal

The capacity of recombinant human interleukin 2 (rl l-l1.2), alone or in combination with recombinant tumor necrosis factor (r-TNFa), to activate murine resident peritoneal macrophages to a tumoricidal state was examined. Resident peritoneal exÃodate cells from C57BL/6 mice were cultured for 18 h with activating agents and washed and the ad herent cells (macrophages) were assessed for cytolytic activity against radiolabeled target tumor cells (HI 4, P815). Under these conditions, rl l-l I 2 alone activated macrophages to a tumoricidal state in a concen tration dependent fashion. Neither murine nor human r-TNFa alone had any activating effect but, when combined with rll-ll.2, further stimulated rH-IL2-inducible responses. Using polymyxin B, it was shown that macrophage activation was not due to an inadvertent lipopolysaccharide contamination of the r-TNFa or r11-11.2preparations. It was also unlikely that target cell lysis was a direct result of increased TNFa production by rll-II 2 stimulated macrophages since PHIS is totally resistant to lysis by r-TNFa. Although the lytic effector function was mediated by adherent cells, nonadherent peritoneal exÃodatecells were required for activation to occur. Furthermore, antisera against murine -r-interferon, when added to activation cultures, reduced the level of cytolytic activity which developed. These data suggest that rHIL2-induced peritoneal macrophage activation requires stimulation of nonadherent cells and is dependent upon -y-interferon mediated