Effect of interferon-gamma, tumor necrosis factor, interleukin-1 and interleukin-6 on the modulation of anti-tumor responses of bone marrow derived macrophages.

Non-adherent bone marrow cells (NABMC) obtained from BALB/c mice were incubated in medium alone or containing granulocyte--macrophage-colony stimulating factor(GM-CSF) or macrophage-colony stimulating factor (M-CSF) for 4 days to obtain bone marrow derived macrophages. Treatment of GM-CSF or M-CSF derived macrophages with interferon-gamma (IFN-gamma) (50 U/ml), tumor necrosis factor (TNF) (500 U/ml), interleukin-1 (IL-1) (200 U/ml) or interleukin-6 (IL-6) (100 U/ml) for 24 h rendered them significantly cytotoxic to different tumor cells. These macrophages also produced enhanced amounts of soluble or membrane associated TNF. Medium derived macrophages showed little cytotoxicity against tumor cells and production of TNF on treatment with TNF, IFN-gamma, IL-1 or IL-6. M-CSF or GM-CSF derived macrophages on treatment with IFN-gamma showed enhanced release of nitrite as compared to medium derived macrophages. TNF, IL-1 or IL-6 did not induce nitrite production in bone marrow derived macrophages. Out of the different combinations tested, only IFN-gamma plus TNF-treated macrophages showed enhancement in nitrite production as compared to that of IFN-gamma alone.