Tumor necrosis factor as a mediator of Mycoplasma orale-induced tumor cell lysis by macrophages

We and other investigators have previously demonstrated that mycoplasmas induce macrophage-mediated lysis of tumor cells, but the mechanism responsible for this process had, thus far, not been clarified. We now report that addition of either viable or heat-killed Mycoplasma orale to murine macrophages induces a cytolytic activity which, due to its neutralization by a specific antiserum against murine cloned recombinant tumor necrosis factor (rTNF), was identified as TNF-mediated. Both thioglycollate-elicited peritoneal macrophages and the normal macrophages cloned from our JBMφ1.1 bone-marrow-derived cell line effectively produced TNF at levels similar to, or higher than, those obtained in the presence of high concentrations of lipopolysaccharide (LPS). Four other mycoplasma species demonstrated a varied capacity to induce TNF production by macrophages. Elevated TNF levels were also observed during macrophage-mediated cytolysis of murine A9 fibrosarcoma cells in the presence of either M. orale or LPS. Addition of the specific antiserum against rTNF at a concentration which neutralized all TNF activity in the co-cultures partially inhibited concomitant A9 cell killing. We can, therefore, conclude that M. orale induces TNF production which is, at least partially, responsible for subsequent tumor cell killing.