Induction of Tumor Necrosis Factor in Mice by Recombinant Human Macrophage Colony-stimulating Factor

Abstract

The effect of recombinant human macrophage colony‐stimulating factor (rhM‐CSF) on endogenous production of tumor necrosis factor (TNF) was investigated in mice. The intravenous injection of lipopolysaccharide (LPS) after the administration of rhM‐CSF via the same route induced the production of endogenous cytotoxic activity in serum as assessed by using TNF‐sensitive miirine L929 cells. The intravenous injection of LPS alone or rhM‐CSF alone did not induce cytotoxic activity. The priming effect of rhM‐CSF was transient and the optimal duration between injections of primer and trigger was 3 h, while the optimal duration between trigger injection and serum sampling was 1 h after LPS injection. Moreover, preinjection of rhM‐CSF enhanced the priming effect of recombinant mouse interferon‐γ. No triggering effect of rhM‐CSF was observed. The cytotoxic activity in the serum was completely neutralized by anti‐mouse TNF‐α polyclonal antibody. These results indicate that rhM‐CSF can be used as a priming agent for endogenous production of TNF in vivo, and raise the possibility of using rhM‐CSF in cancer immunotherapy.