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Tumoricidal Activation of Murine Resident Peritoneal Macrophages by Interleukin 2 and Tumor Necrosis Factor ¹

Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263

The capacity of recombinant human interleukin 2 (rH-IL2), alone or in combination with recombinant tumor necrosis factor (r-TNF), to activate murine resident peritoneal macrophages to a tumoricidal state was examined. Resident peritoneal exudate cells from C57BL/6 mice were cultured for 18 h with activating agents and washed and the adherent cells (macrophages) were assessed for cytolytic activity against radiolabeled target tumor cells (EL4, P815). Under these conditions, rH-IL2 alone activated macrophages to a tumoricidal state in a concentration dependent fashion. Neither murine nor human r-TNF alone had any activating effect but, when combined with rH-IL2, 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-TNF or rH-IL2 preparations. It was also unlikely that target cell lysis was a direct result of increased TNF production by rH-IL2 stimulated macrophages since P815 is totally resistant to lysis by r-TNF. Although the lytic effector function was mediated by adherent cells, nonadherent peritoneal exudate cells were required for activation to occur. Furthermore, antisera against murine -interferon, when added to activation cultures, reduced the level of cytolytic activity which developed. These data suggest that rH-IL2-induced peritoneal macrophage activation requires stimulation of nonadherent cells and is dependent upon -interferon mediated mechanisms.

¹ Supported in part by Grants CA-15142, CA-13038, CA-24538, and CA-16056, awarded by the National Cancer Institute, Department of Health and Human Services, and a travel stipend awarded to S. V. by the Croatian Ministry of Science.

² Medical student, School of Medicine, University of Zagreb, Zagreb, Croatia. Studies carried out during summer visits to Roswell Park Cancer Institute.

³ To whom requests for reprints should be addressed.

Received 1/27/92. Accepted 5/ 6/92.

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