Interferon induction and macrophage activation by a mycovirus double-stranded RNA/tobramycin complex following...

Double-stranded RNA (dsRNA) molecules, generally effective inducers of interferon (IFN), have a weak potency in man apparently because of the presence of a serum RNAase which quickly inactivates extracellular dsRNA. We have discovered that tobramycin, an aminoglycoside, protects Penicillium chrysogenum mycovirus dsRNA (PCMdsRNA) from the degradative action of the nuclease. Exposure of the dsRNA/tobramycin complex to human serum results in some degradation, but still permits the production of significantly high titers of IFN upon injection into mice. Intraperitoneal (i.p.) treatment of CFI mice with both dsRNA and dsRNA/tobramycin complex activated macrophages to inhibit the growth of P815 mastocytoma target cells. Following in vitro treatment with human serum, free dsRNA failed to activate peritoneal macrophages in vivo under conditions where this activity of dsRNA/tobramycin complex was retained. By varying the ratio of moles of tobramycin (as free base) to the moles of RNA phosphorous, toxicity can be minimized, while retaining the biologic activities of dsRNA.