Abstract: |
The effects of prostaglandin E (PGE) and recombinant human interferon-α, -β, and -γ alone and in combination were tested for their effects on the proliferation of human bone marrow granulocyte-macrophage colony-forming units (GM-CFU). When tested alone, both classes of cytokines inhibited GM-CFU proliferation. In combination, PGE and all three types of recombinant interferons synergized in their ability to inhibit GM-CFU proliferation. Progressive enrichment for marrow GM-CFU indicated that the synergistic effects of PGE and interferon were dependent upon the presence of marrow-adherent cells. Studies using conditioned media from marrow-adherent cells prepared in the presence of interferon-α, -β, and -γ indicated that adherent cells produced a soluble factor in the presence of interferons that subsequently synergized with PGE in inhibiting GM-CFU proliferation. Neutralization of this conditioned media with a monoclonal antibody to tumor necrosis factor abrogated the synergistic inhibition of GM-CFU observed in the presence of PGE. The addition of recombinant tumor necrosis factor and PGE to accessory cell-depleted bone marrow resulted in synergistic inhibition of GM-CFU proliferation. |