Macrophage colony stimulating factor (CSF-1) blocks the myeloid suppressive but not the antiviral or antiproliferative activities of murine alpha, beta, and gamma interferons in vitro.
Colony stimulating factors have been shown to antagonize the bone marrow suppressive effects of interferons in vitro. The effect of partially purified murine macrophage colony stimulating factor (CSF-1) was evaluated for its ability to antagonize interferon's bone marrow suppressive effect and was measured for its effect against two other interferon activities. The effect of CSF-1 against interferon's bone marrow suppressive effect was measured in a bone marrow colony growth assay. The effect of CSF-1 against interferon's antiviral activity was measured in single-cycle vesicular stomatitis virus growth experiments. The effect of CSF-1 against interferon's antiproliferative activity was measured in 3-day cell growth kinetics assays using B-16 melanoma cells and J-774 reticulum sarcoma cells of macrophage origin. Each of the three types of interferon (MuIFN-alpha, MuIFN-beta, and MuIFN-gamma) were employed and had common effects, though they differed in the levels of their effective concentrations. Concomitant treatment with CSF-1 and interferon blocked the interferon mediated bone marrow suppression in a dose dependent manner but had no effect on the antiviral or antiproliferative activities of the interferons. Importantly, CSF-1 did not affect interferon's antiproliferative activity against the growth of J-774 reticulum sarcoma cells, even though CSF-1 is a macrophage colony stimulating factor and J-774 cells are of macrophage origin. The results suggest that colony stimulating factors might be employed to specifically protect bone marrow function during interferon therapy while not interfering with interferon's antiviral and antitumor activities.
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D007370:Interferon Type I / Q000037:antagonists & inhibitors; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D007372:Interferons / Q000037:antagonists & inhibitors*; D051379:Mice; D014762:Viral Interference / Q000187:drug effects*
D003115:Colony-Stimulating Factors; D007370:Interferon Type I; D007371:Interferon-gamma; D007372:Interferons