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 (Mφ) and bone marrow cells (BMC). Optimal effects were found after 2 days of in vitro culture of the cells with 50 μg/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 Mφ and BMC was paralleled in vivo by an increase in serum CSF levels, followed by a rise in committed granulocyte and Mφ progenitor cells (GM-CFU-C), nucleated BMC, and blood leukocytes of myelomonocytic origin. Poly(I,C)-LC at doses >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 μg/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 μg/ml poly(I,C)-LC in agar cultures induced in ∽45% of the leukemic colonies a differentiation into granulocytes and/or Mφ. 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.
Received June 11, 1985; accepted June 11, 1985.
Address correspondence and reprint requests to Dr. E. Schlick at Lymphokines Section, Laboratory of Molecular Immunoregulation, Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute-Frederick Cancer Research Facility, Building 567, Frederick, MD 21701, U.S.A.
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