Inhibition of colony-stimulating factor-stimulated macrophage proliferation by tumor necrosis factor-α, IFN-γ, and lipopolysaccharide is not due to a general loss of responsiveness to growth factor

Abstract

The role of stimulatory factors, such as the CSF, in the regulation of hemopoiesis has been extensively documented. Less is known of the negative regulators of hemopoiesis. In this report, we show that the macrophage activating agents, TNF-α, IFN-γ, and LPS, are all potent inhibitors of CSF-1-stimulated murine bone marrow-derived macrophage (BMM) DNA synthesis and increase in cell numbers. The inhibitory effects of TNF-α and IFN-γ do not appear to be due to endotoxin contamination in the recombinant cytokine preparations. The inhibition of proliferation is reversible and is not due to a general loss of growth factor responsiveness, inasmuch as the three agents do not inhibit CSF-1-stimulated..