Abstract
Immunomodulators were tested for their ability to stimulate proliferation and biologic activity of ameboid microglia. Only the colony-stimulating factors (CSFs), multipotential-CSF (multi-CSF) and granulocyte/macrophage-CSF (GM-CSF), were potent mitogens for microglia. Other immunomodulators, including interleukin-1, interleukin-2, interferon gamma, tumor necrosis factor, or granulocyte-CSF (G-CSF), had no effect upon microglial growth in vitro. Multi-CSF or GM-CSF were also observed to induce more rapid phagocytosis of polystyrene microspheres by cultured ameboid cells. In order to determine which immunomodulators alter brain inflammatory responses in vivo, we infused recombinant forms of GM-CSF, multi-CSF, macrophage-CSF, or G-CSF into the cerebral cortex of rats. Within 48 hr after infusion multi-CSF or GM-CSF stimulated the appearance of large numbers of mononuclear phagocytes at the site of injection. These same factors also accelerated the clearance of polystyrene microspheres from the brain. Our observations indicate that certain classes of immunomodulators which are mitogens and activators of ameboid microglia in vitro amplify the inflammatory response of the CNS in vivo by action upon intrinsic brain mononuclear phagocytes.