Effects of poly(I,C)-LC on growth and differentiation of normal and malignant myelopoietic progenitor cells.

Polyriboinosinic-polycytidylic acid with poly-L-lysine stabilized with carboxymethylcellulose [poly(I,C)-LC] augmented, in a dose- and time-dependent manner, secretion of colony-stimulating factor (CSF) by peritoneal macrophages (M phi) and bone marrow cells (BMC). Optimal effects were found after 2 days of in vitro culture of the cells with 50 micrograms/ml of poly(I,C)-LC or 14 h to 3 days after a single intraperitoneal injection of 1-2 mg/kg of poly(I,C)-LC into normal mice. The increase in CSF secretion by M phi and BMC was paralleled in vivo by an increase in serum CSF levels, followed by a rise in committed granulocyte and M phi progenitor cells (GM-CFU-C), nucleated BMC, and blood leukocytes of myelomonocytic origin. Poly(I,C)-LC at doses greater than 4 mg/kg, however, were strongly myelosuppressive. In vitro treatment of undifferentiated myelomonocytic leukemia cells from the WEHI-3B cell line with 10-1,000 micrograms/ml of poly(I,C)-LC resulted in a significant increase in CSF secretion by the leukemic cells and a concomitant inhibition of their proliferation. Incubation of cells from the WEHI-3B D+ subline, which differentiate in response to GM-CSF or G-CSF, with 50-100 micrograms/ml poly(I,C)-LC in agar cultures induced in approximately 45% of the leukemic colonies a differentiation into granulocytes and/or M phi. Poly(I,C)-LC, however, had no effect on differentiation of cells from the CSF unresponsive WEHI-3B D- subline. The CSF-inducing biological response modifier poly(I,C)-LC thus has the potential to stimulate growth and differentiation of normal, as well as differentiation of malignant myelopoietic progenitor cells.