An Inhibitor of Cell Proliferation Released by Cultures of Macrophages

Culture fluids from mouse peritoneal exudate cells inhibited (3)H]thymidine incorporation by, and proliferation of, EL-4 leukemia cells, 3T3 cells, and mitogen-stimulated spleen lymphocytes. Inhibited EL-4 leukemia cells recovered their normal proliferative capacity when washed and incubated in normal medium. The inhibitory activity resided in a low-molecular-weight substance that could be absorbed by incubation with the tumor cells. This substance was dialyzable and resistant to tryptic digestion and phosphodiesterase treatment. The mononuclear phagocytes in the peritoneal exudate seemed to be the source of the inhibitor. The inhibitory material was found in the same amounts in exudates of normal mice or mice injected with peptone or infected with Listeria monocytogenes; spleen cells adherent to plastic released the inhibitor but in lesser amount. We suggest that this inhibitor may contribute to the deleterious effects found when various cells, including neoplastic ones, are cultured in the presence of macrophages.