Secretion of colony-stimulating factors by human monocytes and bone marrow cells after in vitro treatment with biological response modifiers.

The results of this study indicate that human interferons (hIFNs) may have bimodal effects in vitro on human myelopoiesis. Low concentrations of hIFN alpha (1-10 U/ml), hIFN beta (1-100 U/ml), and hIFN gamma (1 U/ml) stimulated in vitro increased secretion of colony-stimulating factors (CSF) by human blood monocytes, which induced growth and differentiation of granulocyte-macrophage progenitor cells. High concentrations of hIFNs alpha, beta, gamma (greater than 100 U/ml), however, had direct antiproliferative effects on granulocyte-macrophage progenitors. Both effects could be blocked by monoclonal antibodies against hIFN alpha and hIFN gamma, as well as by heteroantiserum against hIFN beta. Human IFNs did not appear to be involved in mediating the response to the chemically defined biological response modifiers (BRMs) poly ICLC (polyriboinosinic-polycytidylic acid poly-L-lysine) and BM 41.332 (2-cyano-1-[(2-methoxy-6-methyl-pyridin-3yl)-methyl]-aziridine), since neutralizing antibodies against the human IFNs (anti-IFN alpha, beta, gamma) did not block the poly ICLC and BM 41.332-induced secretion of CSF by human blood monocytes. In contrast to hIFNs, poly ICLC and BM 41.332 also stimulated adherent human mononuclear bone marrow cells to secrete CSF, which induced growth and differentiation of nonadherent granulocyte-macrophage progenitors. The studies presented here thus support the concept that selected BRMs might be useful to stimulate in vivo secretion of myelopoietic growth factors and thereby promote granulocyte and monocyte/macrophage functions.