Production of an anti-tumour cytotoxin by human monocytes

Human monocytes incubated in vitro for 20 hr at 37 degrees release a factor which is cytotoxic to a number of human and murine tumour cell lines: untransformed cells appear to be less susceptible. A similar factor is produced under comparable conditions by myelomonocytic leukaemic cells and by macrophages derived from monocytes by in vitro culture for 8 days. Maximum production of the factor occurred in the presence of foetal calf serum or autologous plasma and endotoxin. The factor is newly synthesized in culture as its production is reduced if the monocytes are treated with cycloheximide or actinomycin D or incubated at lower temperatures. Freshly isolated monocytes do not release the factor on freeze--thaw or hypotonic lysis. The monocyte cytotoxin has apparent molecular weights of 34,000 on Ultrogel AcA54 gel filtration and 140,000 on gradient polyacrylamide gel electrophoresis; it has beta 2--gamma 1 electrophoretic mobility in polyacrylamide gel and does not appear to be C3a or arginase.