CYTOKINE PRODUCTION-SUPPRESSIVE EFFECT BY MACROPHAGE-COLONY-STIMULATING FACTOR (M-CSF)

Macrophage colony-stimulating factor (M-CSF) is a protein which is nec essary for proliferation and differenciation of monocyte-macrophage pr ecursor cells. We examined the effect of M-CSF on the cytokine product ion using BCG sensitized mice in vivo. On Day 0, BCG 1 mg/mouse was in jected via the tail vein. Starting from Day 2, M-CSF 30 mu g/mouse (1 X 10(5)U/mg) was injected every 2 days for a total of six times (Day 2 , 4, 6. 8, 10 and 12). On Day 14, LPS 25 mu g/mouse was injected via t he tail vein, and Interferon (IFN)/Tumor necrosis factor-alpha (TNF-al pha) in serum were determined. The productions of IFN and TNF-alpha we re suppressed significantly. These cytokine production-suppressive eff ects of M-CSF were found also in the in vitro experimental system usin g spleen cells collected. On Day 14, spleen cells were collected and a djusted to 5 X 10(6) cells/ml. 20 mu g of LPS was added to 2ml of sple en cells and they were incubated in a CO2 incubator for 24 hours. IFN and TNF-alpha in the supernatant were determined. In the experiment us ing nude mice, the cytokine suppressive effect of M-CSF was not observ ed. MLR test was performed with spleen cells of C57BL/6 treated with M -CSF as the resporder cells, and spleen cells of C3H were treated with mitomycin C as the stimulator cells. MLR was suppressed significantly by administration of M-CSF. These results might possibly reflect the actual effect of M-CSF in the living body, and the T-cell and cellular immunity might be concerned with the mechanism of the cytokine produc tion-suppressive effect of M-CSF.