Induction of tumor necrosis factor in mice by recombinant human macrophage colony-stimulating factor.
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 murine 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-gamma. No triggering effect of rhM-CSF was observed. The cytotoxic activity in the serum was completely neutralized by anti-mouse TNF-alpha 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.
Sakurai
T
T
Biochemical Research Laboratory, Morinaga Milk Industry Co., Ltd., Kanagawa.
Suzu
S
S
Yamada
M
M
Yanai
N
N
Kawashima
T
T
Hatake
K
K
Takaku
F
F
Motoyoshi
K
K
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma